p27

Summary

Gene Symbol: p27
Description: cyclin-dependent kinase inhibitor 1B (p27, Kip1)
Alias: CDKN4, KIP1, MEN1B, MEN4, P27KIP1
Species: human

Top Publications

  1. pmc Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans
    Natalia S Pellegata
    Institutes of Pathology, GSF National Research Center for Environment and Health, 85764 Neuherberg, Germany
    Proc Natl Acad Sci U S A 103:15558-63. 2006
  2. ncbi The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis
    Jiyong Liang
    Department of Molecular Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Nat Cell Biol 9:218-24. 2007
  3. pmc Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation
    Carlos le Sage
    Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    EMBO J 26:3699-708. 2007
  4. ncbi p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion
    Gustavo Baldassarre
    Oncologia Sperimentale 2, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS, Aviano 33081, Italy
    Cancer Cell 7:51-63. 2005
  5. pmc Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states
    Sunita K Agarwal
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 1802, USA
    J Clin Endocrinol Metab 94:1826-34. 2009
  6. doi MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1.)
    M T Gómez-Casares
    Servicio de Hematología and Unidad de Investigación, Hospital Universitario Dr Negrin, Las Palmas, Spain
    Oncogene 32:2239-46. 2013
  7. pmc Role of T198 modification in the regulation of p27(Kip1) protein stability and function
    Monica Schiappacassi
    Division of Experimental Oncology 2, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
    PLoS ONE 6:e17673. 2011
  8. ncbi Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia
    Marianthi Georgitsi
    Department of Medical Genetics, University of Helsinki, Finland
    J Clin Endocrinol Metab 92:3321-5. 2007
  9. ncbi Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer
    Daniel G Rosen
    Departments of Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Clin Cancer Res 11:632-7. 2005
  10. ncbi SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    A C Carrano
    Department of Pathology, New York University Medical Center, New York 10016, USA
    Nat Cell Biol 1:193-9. 1999

Detail Information

Publications267 found, 100 shown here

  1. pmc Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans
    Natalia S Pellegata
    Institutes of Pathology, GSF National Research Center for Environment and Health, 85764 Neuherberg, Germany
    Proc Natl Acad Sci U S A 103:15558-63. 2006
    ..identification of a homozygous frameshift mutation in Cdkn1b, encoding the cyclin-dependent kinase inhibitor p27(Kip1). As a consequence of the mutation, MENX-affected rats show dramatic reduction in p27(Kip1) protein...
  2. ncbi The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis
    Jiyong Liang
    Department of Molecular Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Nat Cell Biol 9:218-24. 2007
    ..We present evidence that the cyclin-dependent kinase inhibitor p27(Kip1), is phosphorylated at Thr 198 downstream of the Peutz-Jeghers syndrome protein-AMP-activated protein kinase (LKB1-..
  3. pmc Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation
    Carlos le Sage
    Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    EMBO J 26:3699-708. 2007
    ..novel functional genetic approach and identified miR-221 and miR-222 (miR-221&222) as potent regulators of p27(Kip1), a cell cycle inhibitor and tumor suppressor...
  4. ncbi p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion
    Gustavo Baldassarre
    Oncologia Sperimentale 2, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS, Aviano 33081, Italy
    Cancer Cell 7:51-63. 2005
    ..Here, we report that cytoplasmic expression of p27(kip1) affects microtubule (MT) stability following cell adhesion on extracellular matrix (ECM) constituents...
  5. pmc Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states
    Sunita K Agarwal
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 1802, USA
    J Clin Endocrinol Metab 94:1826-34. 2009
    ..However, the prevalence of identifiable germline MEN1 mutations in familial MEN1 cases is only 70%. Some cases may have a germline mutation in another gene such as the p27 cyclin-dependent kinase inhibitor (CDKI).
  6. doi MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1.)
    M T Gómez-Casares
    Servicio de Hematología and Unidad de Investigación, Hospital Universitario Dr Negrin, Las Palmas, Spain
    Oncogene 32:2239-46. 2013
    ..We found that imatinib upregulated the cell cycle inhibitor p27(KIP1) (p27) in a time- and -concentration dependent manner, and that the extent of imatinib-mediated differentiation was ..
  7. pmc Role of T198 modification in the regulation of p27(Kip1) protein stability and function
    Monica Schiappacassi
    Division of Experimental Oncology 2, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
    PLoS ONE 6:e17673. 2011
    The tumor suppressor gene p27(Kip1) plays a fundamental role in human cancer progression. Its expression and/or functions are altered in almost all the different tumor histotype analyzed so far...
  8. ncbi Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia
    Marianthi Georgitsi
    Department of Medical Genetics, University of Helsinki, Finland
    J Clin Endocrinol Metab 92:3321-5. 2007
    ..Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two acromegalic patients.
  9. ncbi Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer
    Daniel G Rosen
    Departments of Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Clin Cancer Res 11:632-7. 2005
    The cyclin-dependent kinase inhibitor p27(kip1) regulates cellular progression from G(1) to S phase. Several studies have shown that loss of p27(kip1) protein expression is associated with disease progression in various malignancies...
  10. ncbi SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    A C Carrano
    Department of Pathology, New York University Medical Center, New York 10016, USA
    Nat Cell Biol 1:193-9. 1999
    Degradation of the mammalian cyclin-dependent kinase (CDK) inhibitor p27 is required for the cellular transition from quiescence to the proliferative state...
  11. pmc Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells
    Dong Wan Seo
    Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 1500, USA
    J Biol Chem 281:3711-21. 2006
    ..G1 growth arrest in human endothelial cells through de novo synthesis of the cyclin-dependent kinase inhibitor p27Kip1. TIMP-2-mediated inhibition of Cdk4 and Cdk2 activity is associated with increased binding of p27Kip1 to these ..
  12. ncbi CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma
    Adam S Kibel
    Departments of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cancer Res 63:2033-6. 2003
    ..nucleotide polymorphic variants in the 3'-untranslated region of CDKN1A (p21(cip1)) and in codon 109 of CDKN1B (p27(kip1)) for association with advanced prostate cancer in a European-American population...
  13. pmc A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization
    Sara Molatore
    Institute of Pathology, Helmholtz Zentrum Munchen, 85764 Neuherberg, Germany
    Hum Mutat 31:E1825-35. 2010
    ..Recently, mutations in CDKN1B,encoding the cyclin-dependent kinase (Cdk) inhibitor p27, were identified in patients having a MEN1-like phenotype but no MEN1 gene mutations...
  14. doi Inverse correlation between Skp2 and p27(Kip1) in normal endometrium and endometrial carcinoma
    Tsutomu Miyamoto
    Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan
    Gynecol Endocrinol 26:220-9. 2010
    Cyclin-dependent-kinase (cdk) inhibitor, p27(Kip1) (p27), has been shown to participate in progestin-induced growth suppression of normal endometrial glands...
  15. doi CaMKII phosphorylates serine 10 of p27 and confers apoptosis resistance to HeLa cells
    Ryutaro Kajihara
    Department of Immunology and Hematology, Division of Health Sciences, Faculty of Life Sciences, Kumamoto University, Japan
    Biochem Biophys Res Commun 401:350-5. 2010
    ..CaMKII phosphorylation and the expression of p27 were increased in DN-PP6 transfectants...
  16. ncbi Progression of LNCaP prostate tumor cells during androgen deprivation: hormone-independent growth, repression of proliferation by androgen, and role for p27Kip1 in androgen-induced cell cycle arrest
    J M Kokontis
    Ben May Institute for Cancer Research, University of Chicago, Illinois 60637, USA
    Mol Endocrinol 12:941-53. 1998
    ..the cyclin-dependent kinase (cdk) inhibitor p21waf1/cip1 in 104-R1 cells, while expression of the cdk inhibitor p27Kip1 was persistently induced by androgen in both 104-R1 and 104-R2 cells...
  17. ncbi MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle
    Rosa Visone
    Dipartimento di Biologia e Patologia Cellulare e Molecolare c o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facolta di Medicina e Chirurgia, Universita degli Studi di Napoli Federico II, Via Pansini, 5, 80131 Naples, Italy
    Endocr Relat Cancer 14:791-8. 2007
    ..Bioinformatic analysis proposed the p27(Kip1) protein, a key regulator of cell cycle, as a candidate target for the miR-221/222 cluster...
  18. pmc Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization
    Maria Letizia Motti
    Dipartimento di Biologia e Patologia Cellulare e Molecolare L Califano, Universita di Napoli Federico II, Via S Pansini 5, 80131 Napoli, Italy
    Am J Pathol 166:737-49. 2005
    Functional inactivation of the tumor suppressor p27(kip1) in human cancer occurs either through loss of expression or through phosphorylation-dependent cytoplasmic sequestration...
  19. pmc A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors
    Gustavo A Miranda-Carboni
    Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
    Genes Dev 22:3121-34. 2008
    Loss of the CDK inhibitor p27(KIP1) is widely linked with poor prognosis in human cancer...
  20. ncbi Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence
    J Lin
    Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Oncogene 20:2000-9. 2001
    ..rat fibroblast, only Cdk6-D3 retains kinase activity due mainly to its ability to evade inhibition by p27(KIP1) and p21(CIP1) with a resemblance to viral cyclin-bound Cdk6...
  21. pmc Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases
    Abdullah Yalcin
    Division of Medical Oncology Molecular Targets Group, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA
    J Biol Chem 284:24223-32. 2009
    ..cyclin-dependent kinase (Cdk)-1, Cdc25C, and cyclin D3 and decreased the expression of the cell cycle inhibitor p27, a universal inhibitor of Cdk-1 and the cell cycle...
  22. pmc Promotion of cytoplasmic mislocalization of p27 by Helicobacter pylori in gastric cancer
    S Wen
    Department of Medicine, Division of Gastroenterology, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
    Oncogene 31:1771-80. 2012
    The cyclin-dependent kinase (CDK) inhibitor p27 has an important role in cell cycle regulation. Reduced expression of p27 is commonly associated with poor prognosis in many malignancies, including gastric cancer...
  23. ncbi Mutational analysis of the cell cycle inhibitor Kip1/p27 in childhood leukemia
    E A Markaki
    Department of Pediatric Hematology Oncology, University of Crete, Medical School, Heraklion Crete, Greece
    Pediatr Blood Cancer 47:14-21. 2006
    ..b>Kip1/p27 is the main cyclin-dependent kinase inhibitor, which arrests cell division inhibiting G1-S transition...
  24. ncbi Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle
    S Coats
    Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA
    Science 272:877-80. 1996
    ..Murine Balb/c-3T3 fibroblasts deprived of serum mitogens accumulated the cyclin-dependent kinase (CDK) inhibitor p27Kip1. This was correlated with inactivation of essential G1 cyclin-CDK complexes and with cell cycle arrest in G1...
  25. doi Undifferentiated embryonic cell transcription factor-1 (UTF1) inhibits the growth of cervical cancer cells by transactivating p27Kip1
    Xiao Ling Wu
    Department of Reproductive Medicine, First Affiliated Hospital, Xi an Jiaotong University of Medical College, Xi an, Shaanxi 710061, China
    Carcinogenesis 34:1660-8. 2013
    ..in vitro and tumorigenesis in vivo through attenuating cell cycle arrest via increasing the level of p27 (Kip1) ...
  26. pmc The cell cycle inhibitor p27Kip¹ controls self-renewal and pluripotency of human embryonic stem cells by regulating the cell cycle, Brachyury and Twist
    Cristina Menchon
    Center of Regenerative Medicine in Barcelona Barcelona, Spain
    Cell Cycle 10:1435-47. 2011
    ..We identified that the protein expression of the p27(Kip)¹ cell cycle inhibitor is low in hESC cells and increased with differentiation...
  27. doi Cytoplasmic p27 expression is an independent prognostic factor in ovarian cancer
    Timothy J Duncan
    Academic and Clinical Department of Oncology, University of Nottingham, Nottingham, UK
    Int J Gynecol Pathol 29:8-18. 2010
    Dysregulation of the cell cycle is an important prerequisite for cancer development. p27 has an established role in cell cycle control and hence may be disrupted during carcinogenesis...
  28. pmc Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer
    Inke Timmerbeul
    Department of Gastroenterology, Hepatology, and Endocrinology, Institute for Molecular Biology, Department of Hematology and Oncology, Institute for Pathology, Hannover Medical School, D 30625 Hannover, Germany
    Proc Natl Acad Sci U S A 103:14009-14. 2006
    Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality...
  29. doi c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor
    Vidyalakshmi Chandramohan
    Department of Biochemistry, Boston University Medical School, 715 Albany Street, Boston, Massachusetts 02118, USA
    J Cell Biochem 104:2091-106. 2008
    The p27(Kip1) (p27) cyclin-dependent kinase inhibitor and c-Myc oncoprotein play essential roles in control of cell cycle progression and apoptosis...
  30. pmc Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein
    Abdelmajid Sabile
    Institute of Cell Biology, ETH Honggerberg, 8093 Zurich, Switzerland
    Mol Cell Biol 26:5994-6004. 2006
    Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 provides a powerful route for enforcing normal progression through the mammalian cell cycle...
  31. pmc Mitogenic regulation of p27(Kip1) gene is mediated by AP-1 transcription factors
    Ekta Khattar
    Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India
    J Biol Chem 285:4554-61. 2010
    The abundance of cyclin-dependent kinase inhibitor p27(Kip1) during the cell cycle determines whether cells will proliferate or become quiescent...
  32. doi Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes in multiple endocrine neoplasia (MEN1) syndrome patients without any detectable MEN1 gene mutations
    Susana Igreja
    Department of Endocrinology, Barts and the London School of Medicine, London, UK
    Clin Endocrinol (Oxf) 70:259-64. 2009
    ..endocrine tumours, a phenotypic overlap of both MEN1 and MEN2, has been reported to have a homozygous germline p27 (CDKN1B) mutation...
  33. doi Combined PTEN and p27kip1 protein expression patterns are associated with obesity and prognosis in endometrial carcinomas
    Athanassios Dellas
    Department of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
    Clin Cancer Res 15:2456-62. 2009
    Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) and p27(kip1) proteins are key players of the Akt pathway, which is nutritionally regulated by insulin receptor signaling and influenced by estrogens...
  34. pmc Somatic mutation and germline sequence abnormalities in CDKN1B, encoding p27Kip1, in sporadic parathyroid adenomas
    Jessica Costa-Guda
    Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030 3101, USA
    J Clin Endocrinol Metab 96:E701-6. 2011
    ..CDKN1B, encoding cyclin-dependent kinase inhibitor p27(kip1), has recently been implicated in a multiple endocrine tumor phenotype in rats and, rarely, in a human familial ..
  35. ncbi Molecular dissection of the interaction between p27 and Kip1 ubiquitylation-promoting complex, the ubiquitin ligase that regulates proteolysis of p27 in G1 phase
    Shuhei Kotoshiba
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582
    J Biol Chem 280:17694-700. 2005
    ..We recently identified a novel ubiquitin ligase, KPC (Kip1 ubiquitylation-promoting complex), consisting of KPC1 and KPC2, which regulates the ubiquitin-dependent degradation ..
  36. pmc A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression
    Pradip K Majumder
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 14:146-55. 2008
    ..In luminal epithelial cells of Akt-driven PIN, we show the concomitant induction of p27(Kip1) and senescence...
  37. ncbi Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival
    Guang Yang
    Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA
    Clin Cancer Res 8:3419-26. 2002
    ..regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis in both in vitro and in vivo models...
  38. doi MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma
    F Fornari
    1Dipartimento di Medicina Interna e Gastroenterologia e Centro di Ricerca Biomedica Applicata, Universita di Bologna, Policlinico S Orsola, Bologna, Italy
    Oncogene 27:5651-61. 2008
    ..One proven target of miR-221 is CDKN1B/p27, whose downregulation affects HCC prognosis...
  39. pmc p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2
    Isabel Chu
    Braman Family Breast Cancer Institute of the University of Miami Sylvester Comprehensive Cancer Center and Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
    Cell 128:281-94. 2007
    The kinase inhibitor p27Kip1 regulates the G1 cell cycle phase. Here, we present data indicating that the oncogenic kinase Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88...
  40. ncbi Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export
    Noriko Ishida
    Departments of Molecular and Cellular Biology and Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    J Biol Chem 277:14355-8. 2002
    Phosphorylation of the cyclin-dependent kinase inhibitor p27(Kip1) has been thought to regulate its stability. Ser(10) is the major phosphorylation site of p27(Kip1), and phosphorylation of this residue affects protein stability...
  41. pmc C-terminal phosphorylation controls the stability and function of p27kip1
    Uta Kossatz
    Institute for Molecular Biology, Hannover Medical School, Hannover, Germany
    EMBO J 25:5159-70. 2006
    ..Degradation of p27kip1 is known to be a central component of this process as it allows controlled activation of cdk2-associated kinase ..
  42. ncbi Cell cycle-dependent caspase-like activity that cleaves p27(KIP1) is the beta(1) subunit of the 20S proteasome
    Winston S Tambyrajah
    School of Life Sciences, University of Sussex, Brighton, UK
    Arch Biochem Biophys 466:186-93. 2007
    ..activity, which we termed KIPase that is implicated in the turnover of the mammalian cell cycle regulator p27(KIP1)...
  43. ncbi p21Cip1 and p27Kip1 induce distinct cell cycle effects and differentiation programs in myeloid leukemia cells
    Maria J Munoz-Alonso
    Grupo de Biología Molecular del Cáncer, Departamento de Biología Molecular y Unidad de Biomedicina Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, 39011 Santander, Spain
    J Biol Chem 280:18120-9. 2005
    The cyclin-dependent kinase (Cdk) inhibitors p21(Cip1) and p27(Kip1) have been proposed to exert redundant functions in cell cycle progression and differentiation programs, although nonoverlapping functions have also been described...
  44. ncbi Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex
    A A Russo
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York 10021, USA
    Nature 382:325-31. 1996
    The crystal structure of the human p27Kip1 kinase inhibitory domain bound to the phosphorylated cyclin A-cyclin-dependent kinase 2 (Cdk2) complex has been determined at 2.3 angstrom...
  45. pmc SKP2 oncogene is a direct MYC target gene and MYC down-regulates p27(KIP1) through SKP2 in human leukemia cells
    Gabriel Bretones
    Departamento de Biologia Molecular, Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria, Consejo Superior de Investigaciones Cientificas, SODERCAN Sociedad para el Desarrollo de Cantabria, 39011 Santander, Spain
    J Biol Chem 286:9815-25. 2011
    SKP2 is the ubiquitin ligase subunit that targets p27(KIP1) (p27) for degradation...
  46. ncbi Down-regulation of p27(Kip1) by two mechanisms, ubiquitin-mediated degradation and proteolytic processing
    M Shirane
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812 8582, Japan
    J Biol Chem 274:13886-93. 1999
    The intracellular level of p27(Kip1), a cyclin-dependent kinase (CDK) inhibitory protein, is rapidly reduced at the G1/S transition phase when the cell cycle pause ceases...
  47. pmc The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells
    Lifang Lu
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA
    BMC Cell Biol 3:22. 2002
    The cyclin-dependent kinase inhibitor p27 is a putative tumor suppressor that is downregulated in the majority of human prostate cancers...
  48. pmc Novel p27(kip1) C-terminal scatter domain mediates Rac-dependent cell migration independent of cell cycle arrest functions
    Sandra S McAllister
    Howard Hughes Medical Institute, University of California San Diego School of Medicine, La Jolla 92093 0686, USA
    Mol Cell Biol 23:216-28. 2003
    ..of HepG2 human hepatocellular carcinoma cells induces cell migration concomitant with increased levels of the p27(kip1) cyclin-cdk inhibitor...
  49. ncbi Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1 phase
    Takumi Kamura
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    Nat Cell Biol 6:1229-35. 2004
    The cyclin-dependent kinase inhibitor p27(Kip1) is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway...
  50. doi Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels
    Daisuke Morishita
    Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, The University of Tokyo, Tokyo, Japan
    Cancer Res 68:5076-85. 2008
    ..family members (Pim1, Pim2, and Pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27(Kip1) at threonine-157 and threonine-198 residues in cells and in vitro...
  51. doi High intracellular content of cyclin-dependent kinase inhibitor p27(Kip1) in early- and intermediate stage B-cell chronic lymphocytic leukemia lymphocytes predicts rapid progression of the disease
    Dariusz Wolowiec
    Department of Hematology, Medical University of Wrocław, Wrocław, Poland
    Eur J Haematol 82:260-6. 2009
    ..chronic lymphocytic leukemia (B-CLL) displayed a high intracellular level of cell cycle inhibitory protein p27(Kip1)...
  52. ncbi Pathway-specific tumor suppression. Reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice, but not in Smad3 mutant mice
    Jeannette Philipp-Staheli
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 90109, USA
    Cancer Cell 1:355-68. 2002
    Expression of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) is frequently reduced in human colorectal cancer, and this correlates with poor patient prognosis...
  53. pmc p27(Kip1) as a prognostic factor in breast cancer: a systematic review and meta-analysis
    Xiaoxiang Guan
    Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People s Republic of China
    J Cell Mol Med 14:944-53. 2010
    The aim of this study was to comprehensively evaluate via a meta-analysis the association between p27 expression and clinical outcome in breast cancer patients...
  54. doi Human papillomavirus 16 E6/E7-immortalized human gingival keratinocytes with epithelial mesenchymal transition acquire increased expression of cIAP-1, Bclx and p27(Kip1)
    Walee Chamulitrat
    Department of Internal Medicine IV, University Heidelberg Hospital, Heidelberg, Germany
    Exp Dermatol 18:1067-9. 2009
    ..We found that EMT cells expressed significantly elevated levels of cIAP-1, Bclx and p27(kip) higher than non-EMT cells...
  55. pmc The function of p27 KIP1 during tumor development
    Jinhwa Lee
    Department of Clinical Lab Science, Dongseo University, Busan 617 716, Korea
    Exp Mol Med 41:765-71. 2009
    ..One CKI of importance is p27(KIP1)...
  56. ncbi Inverse relationship between p27/Kip.1 and the F-box protein Skp2 in human astrocytic gliomas by immunohistochemistry and Western blot
    Davide Schiffer
    Department of Neuroscience, University of Turin, Via Cherasco 15, Turin, Italy
    Neurosci Lett 328:125-8. 2002
    The F-box protein Skp2 regulates G1-S transition by controlling p27/Kip.1. The deregulated expression of p27/Kip.1 plays a critical role in the pathogenesis of many human tumors...
  57. ncbi Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression
    Cheng Han Tsai
    Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang Ming University, Taipei, Taiwan
    Cell Cycle 8:2365-74. 2009
    ..cycle proteins controlling the G(1) phase progression revealed that the cyclin-dependent kinase inhibitor (CKI) p27(kip1) was the primary molecule induced by overexpressed cofilin in a time and dose dependent manner...
  58. pmc Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control
    H Jakel
    Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
    Oncogene 30:3502-12. 2011
    ..In this study, we describe the identification of the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) as a novel JAK2 substrate. JAK2 can directly bind and phosphorylate p27(Kip1)...
  59. pmc WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) delays cellular senescence by promoting p27(Kip1) degradation in human diploid fibroblasts
    Xiaoxiao Cao
    Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University, Health Science Center, Beijing 100191, China
    J Biol Chem 286:33447-56. 2011
    ..Here, we show that the expression patterns of p27(Kip1) and WWP1 are inversely correlated during cellular senescence...
  60. doi Polymorphisms in the p27kip-1 and prohibitin genes denote novel genes associated with melanoma risk in Brazil, a high ultraviolet index region
    Guilherme Francisco
    Experimental Oncology Laboratory, Medical Investigation Laboratory, Unit 24, Department of Radiology
    Melanoma Res 23:231-6. 2013
    ..This study was carried out to evaluate the role of polymorphisms in cell cycle genes such as TP53, p27, CDKN2A, prohibitin, and GADD153 in melanoma risk as well as their influence on known risk factors in a high UV ..
  61. pmc Clinicopathological significance of expression of Tspan-1, Jab1 and p27 in human hepatocellular carcinoma
    Li Chen
    Department of Pathology, Affiliated Hospital, Nantong University, Nantong, China
    J Korean Med Sci 25:1438-42. 2010
    The aim of this study was to investigate the expression of Tspan-1, Jab1 and p27 in human hepatocellular carcinoma (HCC) and their clinicopathological significance...
  62. pmc CDKN1B, encoding the cyclin-dependent kinase inhibitor 1B (p27), is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloid leukemia
    Claudia Haferlach
    MLL, Munich Leukemia Laboratory, Max Lebsche Platz 31, 81377 Munich, Germany
    Haematologica 96:829-36. 2011
    ..Alterations of the short arm of chromosome 12 (12p) occur in various hematologic malignancies and ETV6 and CDKN1B, which are located on 12p, have been implicated as leukemogenic genes of interest...
  63. doi Novel mutations in MEN1, CDKN1B and AIP genes in patients with multiple endocrine neoplasia type 1 syndrome in Spain
    Oihana Belar
    Endocrinology Research Group, Cruces Hospital, CIBERER, Barakaldo, Bizkaia, Spain
    Clin Endocrinol (Oxf) 76:719-24. 2012
    ..Not all patients with MEN1 phenotype present a defect in this gene. Thus, other genes like CDKN and AIP have been showed to be involved in MEN1-like patients...
  64. doi Early mitotic inhibitor-1, an anaphase-promoting complex/cyclosome inhibitor, can control tumor cell proliferation in hepatocellular carcinoma: correlation with Skp2 stability and degradation of p27(Kip1)
    Yunhong Zhao
    Department of Pathology, Nantong University Cancer Hospital, Medical College of Nantong University, Nantong, Jiangsu 226001, PR China
    Hum Pathol 44:365-73. 2013
    ..serum starvation, the expression of Emi1 APC/C substrates (cyclins A, B) and Skp2 was up-regulated, whereas p27(Kip1) was down-regulated...
  65. doi TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression and RhoA activity
    Hyeonjung Kim
    Department of Tumor Biology, Cancer Research Institute, Cell Dynamics Research Center, College of Medicine, Seoul National University, Seoul 151 742, Republic of Korea
    Biochim Biophys Acta 1803:975-82. 2010
    ..However, TM4SF5-facilitated G1/S phase progression was blocked by silencing of p27Kip1 using siRNA or by infection of active RhoA...
  66. ncbi Phosphorylation of Ser72 does not regulate the ubiquitin ligase activity and subcellular localization of Skp2
    Christel Boutonnet
    Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, QC, Canada
    Cell Cycle 9:975-9. 2010
    ..We show here that phosphorylation of Ser72 does not control Skp2 binding to Skp1 and Cul1, has no influence on SCF(Skp2) ubiquitin ligase activity, and does not affect the subcellular localization of Skp2 in a panel of cell lines...
  67. pmc Phosphorylation of Ser72 is dispensable for Skp2 assembly into an active SCF ubiquitin ligase and its subcellular localization
    Tarig Bashir
    Department of Pathology, New York University Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY, USA
    Cell Cycle 9:971-4. 2010
    ..Skp2 is a nuclear F-box protein that targets the CDK inhibitor p27 for ubiquitin- and proteasome-dependent degradation...
  68. pmc Regulation of Skp2 levels by the Pim-1 protein kinase
    Bo Cen
    Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 285:29128-37. 2010
    ..to regulate cell growth is mediated, in part, by the capacity of this protein kinase to control the levels of the p27, a protein that is a critical regulator of cyclin-dependent kinases that mediate cell cycle progression...
  69. doi Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL
    Antosz Halina
    Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland
    Folia Histochem Cytobiol 48:534-41. 2010
    ..We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2, p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately control the ..
  70. ncbi p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer
    Kyriakos Revelos
    Department of Pathology, Evangelismos General Hospital, Athens, Greece
    In Vivo 19:911-20. 2005
    The immunohistochemical expressions (IE) of p27(kip1) and Ki-67 (MIB-1), both involved in cell cycle regulation and cell proliferation, and their ability to predict biochemical failure, were assessed in patients with clinically localized ..
  71. ncbi The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication
    Shriram Nallamshetty
    National Heart, Lung, and Blood Institute, National Institutes of Health, Building 50, Room 4523, 50 Center Drive, Bethesda, MD 20892, USA
    FEBS Lett 579:6529-36. 2005
    ..Here, we report a novel function for the cyclin-dependent kinase inhibitor p27Kip1 in inhibiting DNA replication through its interaction with MCM7, a DNA replication protein that is essential for ..
  72. doi p27Kip1 promotes migration of metastatic hepatocellular carcinoma cells
    Xiao Qi Wang
    Department of Surgery, University of Hong Kong, Hong Kong, SAR, China
    Tumour Biol 29:217-23. 2008
    p27(Kip1) (p27) is a member of the Cip/Kip family of cyclin/cyclin-dependent kinase inhibitors (CKIs), and its CKI-independent function regarding cell motility modulation has been discovered...
  73. ncbi Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity
    M Schreiber
    Department of Biology, McMaster University, Hamilton, Ontario, Canada
    Oncogene 18:1663-76. 1999
    ..vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter...
  74. pmc Loss of cell cycle regulators p27(Kip1) and cyclin E in transitional cell carcinoma of the bladder correlates with tumor grade and patient survival
    J J Del Pizzo
    Division of Urology, Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    Am J Pathol 155:1129-36. 1999
    The cyclin-dependent kinase inhibitor p27(Kip1) is a powerful molecular determinant of cell cycle progression. Loss of expression of p27(Kip1) has been shown to be predictive of disease progression in several human malignancies...
  75. ncbi Association between the V109G polymorphism of the p27 gene and the risk and progression of oral squamous cell carcinoma
    Guojun Li
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Clin Cancer Res 10:3996-4002. 2004
    Abnormalities in p27 may alter cell cycle delay required for DNA repair after exposure to carcinogens...
  76. ncbi Direct binding of the signal-transducing adaptor Grb2 facilitates down-regulation of the cyclin-dependent kinase inhibitor p27Kip1
    Y Sugiyama
    Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma, Nara 630 0101, Japan
    J Biol Chem 276:12084-90. 2001
    ..expression of Jab1/CSN5 induces specific down-regulation of the cyclin-dependent kinase (Cdk) inhibitor p27 (p27(Kip1)) in a manner dependent upon transportation from the nucleus to the cytoplasm...
  77. doi Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia
    G Occhi
    Endocrinology Division, Department of Medical and Surgical Sciences, Via Ospedale, 105, 35128 Padova, Italy
    Eur J Endocrinol 163:369-76. 2010
    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27(KIP1) encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and ..
  78. ncbi Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases
    Matthias Grimmler
    Max Planck Institute of Biochemistry, Am Klopferspitz 18, D 82152 Martinsried, Germany
    Cell 128:269-80. 2007
    b>p27Kip1 controls cell proliferation by binding to and regulating the activity of cyclin-dependent kinases (Cdks). Here we show that Cdk inhibition and p27 stability are regulated through direct phosphorylation by tyrosine kinases...
  79. ncbi High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers
    Mai Shimada
    Department of Biochemistry 1, Hamamatsu University School of Medicine, Higashi ku, Hamamatsu, Shizuoka, Japan
    Cancer Sci 100:866-72. 2009
    Downregulation of the cyclin-dependent kinase inhibitory protein p27 is frequently observed in various cancers due to enhancement of its degradation...
  80. ncbi Inactivation of p27Kip1 by the viral E1A oncoprotein in TGFbeta-treated cells
    A Mal
    Department of Molecular Biology, Cleveland Clinic Research Institute, Ohio 44195, USA
    Nature 380:262-5. 1996
    ..4), inactivation of the cyclin E/A-cdk2 complex by the inhibitory protein p27Kip1 (refs 5-7), and with the accumulation of unphosphorylated retinoblastoma protein...
  81. ncbi Regulation of p27Kip1 by miRNA 221/222 in glioblastoma
    Jana K Gillies
    Ottawa Health Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada
    Cell Cycle 6:2005-9. 2007
    Levels of p27(Kip1), a key negative regulator of the cell cycle, are often decreased in cancer...
  82. pmc MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1
    Tyler E Miller
    Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 283:29897-903. 2008
    ..The protein level of the cell cycle inhibitor p27(Kip1), a known target of miR-221/222, was reduced by 50% in OHT(R) cells and by 28-50% in miR-221/222-overexpressing MCF-..
  83. ncbi PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization
    Incheol Shin
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Nat Med 8:1145-52. 2002
    We have shown a novel mechanism of Akt-mediated regulation of the CDK inhibitor p27(kip1). Blockade of HER2/neu in tumor cells inhibits Akt kinase activity and upregulates nuclear levels of the CDK inhibitor (Kip1)...
  84. ncbi Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer
    Giuseppe Viglietto
    Istituto di Endocrinologia ed Oncologia Sperimentale, CNR c o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Naples, Italy
    Nat Med 8:1136-44. 2002
    The cyclin-dependent kinase inhibitor p27(kip1) is a putative tumor suppressor for human cancer. The mechanism underlying p27(kip1) deregulation in human cancer is, however, poorly understood...
  85. ncbi Prognostic impact of Skp2 and p27 in human breast cancer
    Frank Traub
    Institue of Pathology, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, D 30625, Hannover, Germany
    Breast Cancer Res Treat 99:185-91. 2006
    ..cycle is controlled by cyclin-dependent kinases and one of the key players is the cyclin-dependent kinase inhibitor p27. The F-box protein Skp2 is a regulator of G1-S transition and promotes specifically the ubiquitin-mediated ..
  86. ncbi Low expression of p27(Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma
    Toshiro Migita
    Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan
    Cancer 94:973-9. 2002
    Proliferative activity in tumors depends on regulation of the cell cycle. p27(Kip1) (p27) plays a pivotal role as a negative regulator of the cell cycle...
  87. ncbi Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer
    Ole J Halvorsen
    Department of Pathology, The Gade Institute, Haukeland University Hospital, N 5021 Bergen, Norway
    Clin Cancer Res 9:1474-9. 2003
    Recent experimental work indicates a major role for PTEN and p27 in prostate cancer...
  88. ncbi Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization
    Naoya Fujita
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113 0032, Japan
    J Biol Chem 277:28706-13. 2002
    In many human cancers, the cyclin-dependent kinase inhibitor p27(Kip1) is expressed at low or undetectable levels...
  89. pmc Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc
    J Vlach
    Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland
    EMBO J 15:6595-604. 1996
    We show here that c-Myc antagonizes the cyclin-dependent kinase (CDK) inhibitor p27Kip1. p27 expressed from recombinant retroviruses in Rat1 cells associated with and inhibited cyclin E/CDK2 complexes, induced accumulation of the pRb and ..
  90. pmc Induction of cell cycle arrest by human T-cell lymphotropic virus type 1 Tax in hematopoietic progenitor (CD34+) cells: modulation of p21cip1/waf1 and p27kip1 expression
    Adam Tripp
    Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams St, Syracuse, NY 13210, USA
    J Virol 79:14069-78. 2005
    ..Tax1 induced transcriptional upregulation of the cdk inhibitors p21(cip1/waf1) (p21) and p27(kip1) (p27), and marked suppression of hematopoiesis in immature (CD34(+)/CD38(-)) hematopoietic progenitor cells in ..
  91. ncbi Phosphorylation of p27Kip1 at Thr-157 interferes with its association with importin alpha during G1 and prevents nuclear re-entry
    Incheol Shin
    Department of Cancer Biology and Medicine, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Biol Chem 280:6055-63. 2005
    We have studied mechanisms of Akt-mediated phosphorylation and regulation of cellular localization of p27. Akt phosphorylates Thr-157 in p27 and retains it in the cytosol...
  92. ncbi Downregulation of Skp2 and p27/Kip1 synergistically induces apoptosis in T98G glioblastoma cells
    Sang Hyun Lee
    Cancer Research Institute and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA
    J Mol Med (Berl) 83:296-307. 2005
    ..We downregulated Skp2 in T98G glioblastoma cells using small interfering RNA (siRNA). Downregulation induced p27 and caused growth arrest and apoptosis. Downregulation of both Skp2 and p27 increased apoptosis synergistically...
  93. pmc RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility
    MICHELLE D LARREA
    Department of Biochemistry and Molecular Biology, Braman Family Breast Cancer Institute, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA
    Proc Natl Acad Sci U S A 106:9268-73. 2009
    ..We present evidence that RSK1 drives p27 phosphorylation at T198 to increase RhoA-p27 binding and cell motility...
  94. doi Immunohistochemically detected expression of p27(Kip1) and Skp2 predicts survival in patients with intrahepatic cholangiocarcinomas
    Nozomi Hashimoto
    Departments of Gastroenterological Surgery, Kagawa University, Miki cho, Kita gun, Kagawa, Japan
    Ann Surg Oncol 16:395-403. 2009
    In intrahepatic cholangiocarcinomas (ICCs), the prognostic significance of p27(Kip1), a cyclin-dependent kinase inhibitor, remains controversial, and there have been no studies of degradation pathway associated proteins, S-phase kinase-..
  95. ncbi Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals
    K Polyak
    Howard Hughes Medical Institute, Cell Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021
    Cell 78:59-66. 1994
    We cloned p27Kip1, a cyclin-dependent kinase inhibitor implicated in G1 phase arrest by TGF beta and cell-cell contact...
  96. ncbi p27(kip1) functional regulation in human cancer: a potential target for therapeutic designs
    B Belletti
    Division of Experimental Oncology, Centro di Riferimento Oncologico, Via Pedemontana Occidentale, 12, Aviano 33081, Italy
    Curr Med Chem 12:1589-605. 2005
    ..The present review will deal with the role of one of this CKI, p27(kip1), in human cancer, focusing in particular on the mechanisms underlying its functional inactivation in tumor cells...
  97. ncbi The role of p27Kip1 in proteasome inhibitor induced apoptosis
    Hannes C A Drexler
    Max Planck Institute for Physiological and Clinical Research, Department of Molecular Cell Biology, Bad Nauheim, Germany
    Cell Cycle 2:438-41. 2003
    ..Conflicting results have been reported on the role of the CKI p27Kip1 either in promoting or inhibiting apoptosis mediated by proteasome inhibitors and other drugs...
  98. pmc Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A
    B A Schulman
    Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 95:10453-8. 1998
    ..In the x-ray structure of cyclin A-cdk2-p27, this hydrophobic patch contacts the RNLFG sequence in p27 that is common to a number of substrates and inhibitors ..
  99. ncbi A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1
    C Spruck
    The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Cell 7:639-50. 2001
    ..Here we demonstrate that Cks1 directs the ubiquitin-mediated proteolysis of the CDK-bound substrate p27Kip1 by the protein ubiquitin ligase (E3) SCF(Skp2)...
  100. ncbi The V109G polymorphism of the p27 gene CDKN1B indicates a worse outcome in node-negative breast cancer patients
    Thomas Schondorf
    Department of Natural Sciences, University of Applied Sciences Bonn Rhein Sieg, DE 53359 Rheinbach, Germany
    Tumour Biol 25:306-12. 2004
    Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance...
  101. ncbi Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression
    Benjamin Saltman
    Department of Otolaryngology, Columbia University College of Physicians and Surgeons, New York, NY 10021, USA
    Surgery 140:899-905; discussion 905-6. 2006
    ..The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression...

Research Grants62

  1. B-RAF Regulation of the Cell Cycle in Melanoma
    Andrew E Aplin; Fiscal Year: 2013
    ..cells elevates activation of the MEK-ERK1/2 pathway and regulates two key G1 cell cycle proteins: cyclin D1 and p27Kip1. Our preliminary data indicate that mutant B-RAF signaling and cyclin D1 regulate p27Kip1 via expression of Skp2 ..
  2. CELL CYCLE REGULATION IN NORMAL AND CANCER CELLS
    James M Roberts; Fiscal Year: 2010
    b>p27Kip1 is an evolutionarily conserved protein that regulates both cell proliferation, through inhibitory interactions with cyclins and cyclin-dependent kinases, and cell movement, through its inhibitory interaction with RhoA...
  3. Cell cycle in development and regeneration of the inner ear
    Neil Segil; Fiscal Year: 2011
    ..Changes in the ability of P14 supporting cells to down-regulate p27Kip1 are partly responsible for the block to cell division that results in the lack of regeneration...
  4. Regulation of cyclin D3 in B lymphocyte development
    Marcus R Clark; Fiscal Year: 2013
    ..a novel, lymphoid specific mechanism, controls the subnuclear location of cyclin D3 relative to the inhibitor p27kip1 and the CDK4/Rb effector complex...
  5. Prevention of acute GvHD by inhibition of cdk2
    Vassiliki A Boussiotis; Fiscal Year: 2012
    ..In conjunction with cyclin E, cdk2 phosphorylates the cell cycle inhibitor p27kip1 resulting in ubiquitin-targeted degradation...
  6. Dual role of IL-16 in dysregulated growth of CTCL cells
    William W Cruikshank; Fiscal Year: 2012
    ..regulating degradation of one of the major cyclin kinase inhibitors associated with T cell proliferation, p27kip1. Our preliminary data now indicates that in T cells from CTCL patients there is an initial redistribution of ..
  7. Signal Transduction by the Microtubule Destabilizer, Stathmin/Oncoprotein 18
    Lynne Cassimeris; Fiscal Year: 2012
    ..The other stathmin binding partners, p27Kip1 and STAT3, will be tested for their potential role(s) in regulating cell cycle progression after stathmin ..
  8. Physiologic Regulation of Hematopoiesis by Notch
    Nadia Carlesso; Fiscal Year: 2011
    ..activation of SKP2, the F-box subunit of the SCFskp2 complex that targets the cell cycle inhibitors p27Kip1 and p21Cip1 for degradation, promoting their downregulation and the entry into S-phase...
  9. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
    ..These studies may lead to the development of new drugs and/or dietary components for use in cancer prevention or treatment. ..
  10. The role of cyclin E deregulation in breast tumorigenesis
    ALEXANDER C MINELLA; Fiscal Year: 2010
    ..In addition to high cyclin E expression, reduced expression of the cyclin-dependent kinase inhibitor p27Kip1 has also been found to correlate with poor prognosis in breast cancers...
  11. Signaling Pathways in Hepatic Fibrogenesis
    Bruce Bacon; Fiscal Year: 2005
    ..cell cycle, and is dependent on the balance of positive (cyclins, cyclin-dependent kinases; CDK) and negative (p27Kip1) regulatory cell-cycle proteins...
  12. Regulation of CD8 T Cell Immunity by CDK Inhibitor p27Kip1
    Marulasiddappa Suresh; Fiscal Year: 2012
    ..lymphocytic choriomeningitis virus (LCMV) have shown that genetic deficiency of cyclin dependent kinase inhibitor p27Kip1 not only accelerated the differentiation of memory cells from effector CD8 T cells, but also significantly ..
  13. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..showed that the depletion of polyamines in MYCN-amplified NB cells caused G1 cell cycle arrest and affected p27Kip1 levels, retinoblastoma protein Rb phosphorylation, and most intriguingly, blocked MYCN expression, thus providing ..
  14. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David T Scadden; Fiscal Year: 2010
    ..They defined in detail distinctive phenotypes associated with the genetic deficiency of p21Cip1 (p21), p27Kip1 (p27), p18INK4c (p18) and p16INK4a (p16)...
  15. Mechanisms for cell specific modulation of proliferation and migration
    Thomas S Monahan; Fiscal Year: 2013
    ..1) that MARCKS regulates vascular smooth muscle cell proliferation by up- regulation of the cell cycle inhibitor, p27kip1 2) that MACRKS modulates cell migration by disrupting cellular actin organization and 3) that MARCKS knockout in ..
  16. Controlling VSMC Proliferation and Migration
    Ming Hui Zou; Fiscal Year: 2013
    ..Consistent with this finding, the cell cycle inhibitor, p27Kip1 (p27), was dramatically down-regulated in AMPKa2-knock out (KO) mouse VSMC but not AMPKa1-KO VSMC...
  17. Prostate Cancer: Transition to Androgen - Independence (CA77739)
    James L Mohler; Fiscal Year: 2013
    ..the influence of MAGE-11 and Rb/p107 on Skp2 stimulation of cell proliferation through the degradation of the p27-Kip1 tumor suppressor...
  18. Regulation and Role of Ornithine Decarboxylase in Cell Proliferation and Cancer
    John L Cleveland; Fiscal Year: 2013
    ..by selectively affecting Myc's ability to provoke the degradation of the cyclin- dependent kinase inhibitor p27Kip1, a tumor suppressor that inhibits entry and progression through S-phase...
  19. MECHANISMS OF ARTERIAL GRAFT HEALING
    Alexander W Clowes; Fiscal Year: 2013
    ..We have studied a single nucleotide polymorphism (-838 C>A) in the promoter of the p27Kip1 gene (CDKN1B), an important cyclin-dependent kinase inhibitor, in four separate clinical trials encompassing 3279 ..
  20. Role of Reactive Oxygen Species in B Lymphoma Fate
    Gregory B Carey; Fiscal Year: 2012
    ..g. c-Myc, Akt, CDK2 and p27Kip1)...
  21. Hair Cell Development
    Zheng Yi Chen; Fiscal Year: 2013
    ..Deletion of negative growth genes (Rb1 and p27kip1) led to cell cycle re-entry in embryonic and neonatal inner ear...
  22. Seattle Cancer Consortium Breast SPORE
    Peggy L Porter; Fiscal Year: 2013
    ..Project 1 will apply basic discovery of p27kip1 cell cycle regulation in breast cancer to predict mortality and response to therapy...
  23. Requirements for Normal Rb Function In Vivo
    David W Goodrich; Fiscal Year: 2010
    ..Another possible mechanism involves targeted degradation of Skp2 by pRb and consequent stabilization of p27Kip1. The ability of pRb to regulate E2F transcription factors is genetically separable from its ability to degrade ..
  24. HER-2/IGF-IR cross-talk and Herceptin resistance
    Rita Nahta; Fiscal Year: 2010
    ..HER-2 in this complex is phosphorylated, suggesting cross-talk from IGF-IR to HER-2;2) p27kip1, which lies downstream of both HER-2 and IGF-IR, is downregulated in resistant cells...
  25. Mechanisms of p27Kipl Proteolysis in Cancer Cells
    Xuedong Liu; Fiscal Year: 2012
    Decreased levels of cell cycle inhibitor p27Kip1 due to excessive degradation occur in a variety of aggressive human tumors...
  26. The Anaphase Promoting Complex and Cell Cycle Exit
    Nagi G Ayad; Fiscal Year: 2013
    ..The APC degrades the ubiquitin ligase component Skp2, which allows p27kip1 levels to rise, thereby inducing cell cycle exit...
  27. P27Kipl deficiency, potential promoter of carcinogenesis
    Konstantin Christov Tzelkov; Fiscal Year: 2003
    ..We will examine the feasibility of p27/Kip1 deficiency in transgenic mice for potential use in mammary carcinogenesis studies in chemopreventive studies...
  28. Prevention of Menopause-Related Ovarian Epithelial Cancer
    Elizabeth R Smith; Fiscal Year: 2010
    ..When deletion of the cyclin-dependent kinase inhibitor p27kip1 gene, whose expression is often lost in ovarian cancer, is added to the Wv/Wv genotype, the ovarian tumors ..
  29. Role of Skp2-cyclin A Interaction in Normal Physiology and Cancer
    Liang Zhu; Fiscal Year: 2013
    ..Skp2 is an F-box protein of the SCF(Skp2) ubiquitin ligase complex targeting p27Kip1 for ubiquitination...
  30. TUMORIGENESIS AND NEUROGENESIS OF P27 KIP1 KNOCKOUT MICE
    Li Huei Tsai; Fiscal Year: 1999
    ..This view is supported by the phenotype which we have observed in mice harboring a homozygous deletion of the p27 kip1 gene...
  31. MECHANISM OF RETROCORNEAL FIBROUS MEMBRANE
    EunDuck P Kay; Fiscal Year: 2010
    ..We showed that there are distinct populations of p27Kip1 (p27) that employ differential kinetics of phosphorylation, ubiquitination and degradation, suggesting that CECs ..
  32. Regulation of Vascular Smooth Muscle Cell Proliferation
    Hana Totary Jain; Fiscal Year: 2010
    ..will test the hypothesis that diabetes leads to an overstimulation of the PI3K/Akt/Foxo pathway', decreasing p27Kip1 gene expression, conferring relative rapamycin resistance...
  33. REGULATION OF CELL PROLIFERATION IN THE ORGAN OF CORTI
    Ping Chen; Fiscal Year: 2001
    ..We found that p27Kip1, a cell division inhibitor, plays an essential growth inhibitory role during development of the organ of Corti...
  34. CELL CYCLE IN OLIGODENDROCYTE DEVELOPMENT
    Robin Miskimins; Fiscal Year: 2000
    ..of oligodendrocyte progenitor cells is accompanied by a marked increase in the cyclin dependent kinase inhibitor p27kip1 (and a decrease in cyclin E)...
  35. Gonadotropins &Cox-2 in Ovarian Cancer Prevention
    XIANGXI MIKE XU; Fiscal Year: 2013
    ..Furthermore, addition of oncogenic mutation such as loss of p27kip1 or loss of p53 converts the ovarian adenomas into neoplastic tumors...
  36. Arginase II, A Novel Target in Atherosclerosis
    Lewis H Romer; Fiscal Year: 2013
    ..mediates OxLDL activation of Arg2 through LOX-1 and the following signaling intermediaries: MT1-MMP, p27kip1, RhoA, ROCK, and mDia1...
  37. CONTRACT #N43-CO-95012-616 MONTHS FUNDING -PHASE 1 TOPIC 265 DEVELOPMENT OF SHRN
    Xiao Zeng; Fiscal Year: 2009
    ..Phase I, Develop and screen a focused, FV shRNA collection to identify factors that are involved in the MCL-1 and p27kip1 signaling pathways...
  38. ECM MATRIX, PROTEASE AND MELANOMA PROLIFERATION
    Yves DeClerck; Fiscal Year: 2007
    ..interphase and that this arrest involves a specific up-regulation of the cell cyclin dependent kinase inhibitor p27KIP1 (Henriet et al., PNAS, 97:10026-10031, 2000)...
  39. Regulation of Bladder Smooth Muscle Hyperplasia
    Paul Austin; Fiscal Year: 2007
    ..to varying degrees of resistance to contraction, the candidate has found that the cell cycle control protein p27KIP1 is downregulated by the development of increased tension within the SMC...
  40. MECHANISMS OF CELL CYCLE CONTROL DURING MAMMARY GLAND DE
    Hui Zhang; Fiscal Year: 2001
    ..We found that SKP2 specifically binds to and targets the CDK inhibitor p27Kip1 for ubiquitin- dependent proteolysis during the G1/S transition...
  41. Prostate Cancer Chemoprevention by Inositol Hexaphosphate Efficacy and Mechanism
    Rajesh Agarwal; Fiscal Year: 2010
    ..In PCA cell culture, completed studies by us show that IP6 up- regulates CDKI Kip1/p27 and Cip1/p21 levels together with their increased interaction with CDKs causing inhibition in the kinase ..
  42. Alcohol and Impairment of the Granulopoietic Response to Pneumonia
    Ping Zhang; Fiscal Year: 2010
    ..also activates signal transducer and activator of transcription 3 (STAT3)-cyclin-dependent kinase (CDK) inhibitor p27Kip1 pathway that provides a negative feedback signal to cause G1 cell cycle arrest...
  43. DIET,APOPTOSIS AND COLON CARCINOGENESIS
    Joanne Lupton; Fiscal Year: 2004
    ..Determine in vivo expression of Cox-2, apoptosis, p21waf1/CipI p27kip1, Cyclin Dl, cell proliferation and differentiation as a function of dietary lipid, butyrate, and carcinogen ..
  44. MOLECULAR-GENETIC ANALYSIS OF 3P14 GENOMIC STABILITY
    Harry Drabkin; Fiscal Year: 2006
    ..and JAB 1 has also been shown to regulate nuclear-cytoplasmic transport and proteasome-mediated degradation of p27 kip1, which is characteristically abnormal in RCCs and which has been linked to VHL mutations...
  45. NUTRITIONAL FACTORS IN MAMMALIAN DEVELOPMENT
    Carl Keen; Fiscal Year: 2009
    ..of both P13K and MAPK signaling pathways, which results in the down-regulation of the cell cycle inhibitor, p27/kip1, and the cytosolic sequestration and phosphorylation of the pro-apoptotic protein, BAD...
  46. Nutritional mechanisms and intestinal tumorigenesis
    Leonard Augenlicht; Fiscal Year: 2009
    ..We have determined that intestinal tumor formation in mice with targeted inactivation of the cdk inhibitor p27kip1 is strictly a function of diet: very few tumors form in p27+/- or p27-/- mice fed chow diet, but tumor formation ..
  47. IRREVERSIBLE GROWTH ARREST AND SQUAMOUS DIFFERENTIATION
    BETH HARVAT; Fiscal Year: 2001
    ..p130, p27KiP1 and p16ink4a are growth inhibitory proteins that are up regulated during the multi-step process of squamous ..
  48. Cell cycle control of vascular remodeling
    RICHARD ASSOIAN; Fiscal Year: 2009
    ..find that these positive and negative regulators act largely by controlling levels of the cdk inhibitory protein, p27kip1. Moreover, this convergence is also seen in the regulation of Skp2, the E3 ubiquitin ligase that controls the ..
  49. RETINOIDS FOR TREATMENT OF OVARIAN CARCINOMA
    KENNETH SOPRANO; Fiscal Year: 2007
    ..IRA treatment of CA-OV3 cells resulted in a significant enhancement in the levels of RB-2/p130 and p27kip1 protein...
  50. Cellular regeneration in the organ of Corti
    Jonathan Kil; Fiscal Year: 2003
    ..The cyclin-dependent kinase inhibitor, p27Kip1, is expressed in the supporting cells of mice from birth through adulthood...
  51. p57KIP2 in Hematopoiesis and Leukemogenesis
    JOSEPH SCANDURA; Fiscal Year: 2009
    ..While p21WAF/CIP1 controls normal murine hematopoietic stem cell quiescence, p27KIP1 regulates the pool of more mature progenitors...
  52. P27kip1 as an early effector of pRB function
    Liang Zhu; Fiscal Year: 2004
    ..We therefore hypothesize that p27 is an early effector of pRB function...
  53. Mouse Models of Tumor Progression and Therapy Response
    CHRISTOPHER KEMP; Fiscal Year: 2007
    ..Reduced expression of the cdk inhibitor p27/Kip1 is frequently observed in a wide range of human tumors and this correlates with poor prognosis...
  54. Growth Regulation of the Normal & Malignant Endometrium
    LESLIE GOLD; Fiscal Year: 2003
    ..Smad2/3,that activate genes that block cell cycle progression, such as the cyclin-dependent kinase inhibitor, p27kip1 We have shown that UtE isolated from all grades of ECA escape negative growth control by TGF-b by incurring ..
  55. IMAGING IN RISK ASSESSMENT OF PROSTATE CANCER PATIENTS
    Hedvig Hricak; Fiscal Year: 2010
    ..the expression of key molecular markers known to be important in prostate cancer biology: Ki-67, PTEN, Akt, p27/Kip1, Bax, and Bcl-2...
  56. Pathways in p27-associated hematolymphoid malignancy
    Harry Hwang; Fiscal Year: 2007
    The overall goals of this research proposal are to understand the mechanisms of tumor suppression by the p27kip1 protein in hematopoietic malignancies. P27 is a cyclin-dependent kinase inhibitor that negatively regulates cell division...
  57. Folate Targeted Delivery of a CDKI
    Joseph Reddy; Fiscal Year: 2003
    ..is that folate-targeted liposomes containing a stabilized version of the cyclin dependent kinase inhibitor, p27Kip1, will block tumor cell growth in vivo...
  58. Targeting p27kip1 to Improve Hepatocyte Transplantation
    Erin Ochoa; Fiscal Year: 2009
    In characterizing the cell-cycle regulatory role of the cyclin-dependent kinase inhibitor, p27kip1, it was discovered that p27 knockout mice exhibit pronounced multi-organomegaly with no increased spontaneous carcinogenesis in the liver...
  59. The molecular role of lkaros in leukemogenesis
    Susan Winandy; Fiscal Year: 2009
    ..We have also identified the cell cycle regulator, p27kip1, as a potential genetic target for transcriptional activation by Ikaros...
  60. Mechanism of tumor suppression by p27
    Matthew Fero; Fiscal Year: 2003
    ..Fero to further our understanding of tumor suppression by the cell cycle inhibitor (CKI) gene p27kip1, while making a transition in his career from the position of a mentored researcher to an independent ..
  61. DETAILED ANALYSIS OF P21/CDK2 INTERACTION
    F Germino; Fiscal Year: 2001
    ..domain of p21 to an approximately 35 amino acid region near the gene's 5'end which shares homology with p27Kip1, another CDK inhibitor induced by TGFbeta...
  62. P27Kip1 in Hepatocyte Proliferation
    Liang Zhu; Fiscal Year: 2006
    ..Targeted inactivation of p27 in the mouse results in proportionally enlarged animals with multi-organomegaly...