s phase kinase associated proteins

Summary

Summary: A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.

Top Publications

  1. 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
  2. ncbi Skp2 regulates Myc protein stability and activity
    So Young Kim
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Mol Cell 11:1177-88. 2003
  3. pmc Skp2 is oncogenic and overexpressed in human cancers
    M Gstaiger
    Friedrich Miescher Institut, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
    Proc Natl Acad Sci U S A 98:5043-8. 2001
  4. ncbi The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription
    Natalie von der Lehr
    Department of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden
    Mol Cell 11:1189-200. 2003
  5. ncbi Skp2 protein expression in soft tissue sarcomas
    Andre M Oliveira
    Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    J Clin Oncol 21:722-7. 2003
  6. ncbi Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma
    Frédéric Pène
    Departement d Hematologie, Institut Cochin, INSERM U567, CNRS UMR 8104, IFR 116, Universite Rene Descartes, Paris, France
    Oncogene 21:6587-97. 2002
  7. ncbi p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase
    H Zhang
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 82:915-25. 1995
  8. ncbi F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex
    D Skowyra
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 91:209-19. 1997
  9. pmc F-box protein Skp2: a novel transcriptional target of E2F
    L Zhang
    Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA
    Oncogene 25:2615-27. 2006
  10. ncbi Differential effects of doxorubicin treatment on cell cycle arrest and Skp2 expression in breast cancer cells
    Ortal Bar-On
    Department of Surgery A, Rambam Medical Center, Technion Israel Institute of Technology, Haifa, Israel
    Anticancer Drugs 18:1113-21. 2007

Detail Information

Publications194 found, 100 shown here

  1. 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
    ..Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation...
  2. ncbi Skp2 regulates Myc protein stability and activity
    So Young Kim
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Mol Cell 11:1177-88. 2003
    ..These data suggest that Skp2 functions to connect Myc activity and destruction, and reveal an unexpected oncoprotein connection that may play an important role in controlling cell growth in normal and cancer cells...
  3. pmc Skp2 is oncogenic and overexpressed in human cancers
    M Gstaiger
    Friedrich Miescher Institut, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
    Proc Natl Acad Sci U S A 98:5043-8. 2001
    ..The observations that Skp2 can mediate transformation and is up-regulated during oral epithelial carcinogenesis support a role for Skp2 as a protooncogene in human tumors...
  4. ncbi The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription
    Natalie von der Lehr
    Department of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden
    Mol Cell 11:1189-200. 2003
    ..The results suggest that Skp2 is a transcriptional cofactor for c-Myc and indicates a close relationship between transcription activation and transcription factor ubiquitination...
  5. ncbi Skp2 protein expression in soft tissue sarcomas
    Andre M Oliveira
    Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    J Clin Oncol 21:722-7. 2003
    ..The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated...
  6. ncbi Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma
    Frédéric Pène
    Departement d Hematologie, Institut Cochin, INSERM U567, CNRS UMR 8104, IFR 116, Universite Rene Descartes, Paris, France
    Oncogene 21:6587-97. 2002
    ..Moreover, constitutive activation of this pathway is a frequent event in the biology of MM in vivo and may be more frequently observed in PCL...
  7. ncbi p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase
    H Zhang
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 82:915-25. 1995
    ..The abundance of p45 is greatly increased in many transformed cells. This could result in changes in cell cycle control that contribute to the process of cellular transformation...
  8. ncbi F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex
    D Skowyra
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 91:209-19. 1997
    ..SCF complexes couple protein kinase signaling pathways to the control of protein abundance...
  9. pmc F-box protein Skp2: a novel transcriptional target of E2F
    L Zhang
    Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA
    Oncogene 25:2615-27. 2006
    ..These results reveal Skp2 as a novel target for E2F regulation that is disrupted in several human tumor cell lines...
  10. ncbi Differential effects of doxorubicin treatment on cell cycle arrest and Skp2 expression in breast cancer cells
    Ortal Bar-On
    Department of Surgery A, Rambam Medical Center, Technion Israel Institute of Technology, Haifa, Israel
    Anticancer Drugs 18:1113-21. 2007
    ....
  11. 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
    ..These studies may guide the choice of clinical settings in which pharmacologic inhibitors of the Skp2 pathway might be of therapeutic value...
  12. ncbi Skp2 overexpression is a prognostic factor in patients with ovarian adenocarcinoma
    Kazushi Shigemasa
    Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, Japan
    Clin Cancer Res 9:1756-63. 2003
    ..The purpose of this study was to examine Skp2 expression in epithelial ovarian tumors and to identify the association of Skp2 expression levels with patient survival...
  13. ncbi A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p
    R M Feldman
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Cell 91:221-30. 1997
    ..Taken together, these data illuminate the molecular basis for the G1/S transition in budding yeast and suggest a general mechanism for phosphorylation-targeted ubiquitination in eukaryotes...
  14. pmc Role of the F-box protein Skp2 in lymphomagenesis
    E Latres
    Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, MSB 548, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 98:2515-20. 2001
    ..This study provides evidence of a role for an F-box protein in oncogenesis and establishes SKP2 as a protooncogene causally involved in the pathogenesis of lymphomas...
  15. ncbi Oncogenic properties and prognostic implications of the ubiquitin ligase Skp2 in cancer
    Dan D Hershko
    Department of Surgery and Breast Health Institute, Rambam Health Care Campus and the Technion Israel Institute of Technology, Haifa, Israel
    Cancer 112:1415-24. 2008
    ..Skp2 may be an attractive target for the development of novel interventional therapy...
  16. ncbi Cell cycle-dependent regulation of the Skp2 promoter by GA-binding protein
    Hiroyuki Imaki
    Departments of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    Cancer Res 63:4607-13. 2003
    ..These data suggest that the cell cycle-dependent binding of GABP to the Skp2 promoter plays an important role in the regulation of Skp2 expression and cell cycle progression from G(1) to S phase...
  17. ncbi Negative regulation of SCFSkp2 ubiquitin ligase by TGF-beta signaling
    Wei Wang
    Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA
    Oncogene 23:1064-75. 2004
    ....
  18. 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
    ..1 degradation...
  19. ncbi Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex
    Wenyi Wei
    Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 428:194-8. 2004
    ..As a result, accumulation of SCF(SKP2) requires prior inactivation of APC(CDH1). These findings provide an insight into the orchestration of SCF and APC activities during cell-cycle progression, and into the involvement of the APC in G1...
  20. ncbi High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas
    Y Kudo
    Department of Oral Pathology, Hiroshima University, Faculty of Dentistry, Hiroshima 734-8553, Japan
    Cancer Res 61:7044-7. 2001
    ....
  21. ncbi Degradation of p27(Kip1) at the G(0)-G(1) transition mediated by a Skp2-independent ubiquitination pathway
    T Hara
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    J Biol Chem 276:48937-43. 2001
    ..These results suggest that a polyubiquitination activity in the cytoplasm contributes to the early phase of p27(Kip1) degradation in a Skp2-independent manner, thereby promoting cell cycle progression from G(0) to G(1)...
  22. 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
    ..Here we used the human prostate cancer cell line LNCaP, which undergoes G1 cell cycle arrest in response to androgen, to examine the role of the SKP2 F-box protein in p27 regulation in prostate cancer...
  23. ncbi Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A
    J J Michel
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, 27599 7295, USA
    Cell Growth Differ 9:435-49. 1998
    ..This implies that most cullins may use a SKP1/F-box-independent pathway to facilitate protein degradation...
  24. pmc Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication
    K Nakayama
    Laboratory of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    EMBO J 19:2069-81. 2000
    ....
  25. ncbi Altered S-phase kinase-associated protein-2 levels are a major mediator of cyclic nucleotide-induced inhibition of vascular smooth muscle cell proliferation
    Yih Jer Wu
    Bristol Heart Institute, University of Bristol, United Kingdom
    Circ Res 98:1141-50. 2006
    ..These data demonstrate for the first time that Skp2 is an important factor in VSMC proliferation and its inhibition by cyclic nucleotides...
  26. ncbi Skp2 contains a novel cyclin A binding domain that directly protects cyclin A from inhibition by p27Kip1
    Peng Ji
    Department of Developmental and Molecular Biology, the Albert Einstein Comprehensive Cancer Center and Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 281:24058-69. 2006
    ..These findings reveal a new functional mechanism of Skp2 and a new regulatory mechanism of cyclin A...
  27. 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
    ..The purpose was to evaluate the prevalence of Skp2 and p27 expression and determine whether a combined index has prognostic power in breast carcinomas...
  28. ncbi Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27Kip1 in prostate cancer
    Ofer Ben-Izhak
    Department of Pathology, Rambam Medical Center, Haifa, Israel
    J Urol 170:241-5. 2003
    ..We examined the relationship between p27 and its specific ligase Skp2 in normal and malignant prostate tissues. A possible correlation among the levels of these proteins, tumor grading and clinical state was also investigated...
  29. ncbi The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E
    K H Yeh
    Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA
    Biochem Biophys Res Commun 281:884-90. 2001
    ..The presence of the CDK inhibitor p27(Kip1) also prevented the SKP2-dependent degradation of cyclin E. Our findings suggest that SKP2 regulates cyclin E stability, thus contributing to the control of S phase progression...
  30. 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
    ..These data suggest that induction of Skp2 may be causally linked with decreased levels of p27 in prostate cancer and implicate PTEN in the regulation of Skp2 expression in vivo, as previous tissue culture experiments have suggested...
  31. ncbi Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase
    Tarig Bashir
    Department of Pathology, MSB 599, New York University School of Medicine, and New York University Cancer Institute, 550 First Avenue, New York, New York 10016, USA
    Nature 428:190-3. 2004
    ..Thus, the induction of Skp2 and Cks1 degradation in G1 represents a principal mechanism by which APC/C(Cdh1) prevents the unscheduled degradation of SCF(Skp2-Cks1) substrates and maintains the G1 state...
  32. ncbi Biological significance of p27 and Skp2 expression in renal cell carcinoma. A systematic analysis of primary and metastatic tumour tissues using a tissue microarray technique
    Cord Langner
    Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria
    Virchows Arch 445:631-6. 2004
    ..In conclusion, p27 and Skp2 proved to be additional biomarkers in renal cancer pathology with both prognostic and diagnostic impact...
  33. ncbi Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis
    Yoo Hong Min
    Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    Clin Cancer Res 10:5123-30. 2004
    ..However, the clinical significance of Skp2 in patients with acute myelogenous leukemia (AML) remains unknown...
  34. pmc In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation
    Roberto Piva
    Department of Pathology and NYU Cancer Institute Division of Hematopathology, New York University School of Medicine, New York, New York 10016, USA
    Mol Cell Biol 22:8375-87. 2002
    ..Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation...
  35. ncbi Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase
    Bing Hao
    Howard Hughes Medical Institute, New York, New York 10021, USA
    Mol Cell 20:9-19. 2005
    ..The structure and biochemical data support the proposed model that Cdk2-cyclin A contributes to the recruitment of p27(Kip1) to the SCF(Skp2)-Cks1 complex...
  36. ncbi High expression of skp2 correlates with poor prognosis in endometrial endometrioid adenocarcinoma
    Yuko Kamata
    Department of Clinical Cytology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan
    J Cancer Res Clin Oncol 131:591-6. 2005
    ..This study aimed to investigate the correlation of skp2 expression with the expression of p27 and other cell cycle regulators, and clinicopathological parameters in endometrial endometrioid adenocarcinoma...
  37. ncbi A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase
    N P Malek
    Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA
    Nature 413:323-7. 2001
    ..Our efforts to explain this unexpected result led to the discovery of a second proteolytic pathway for controlling p27, one that is activated by mitogens and degrades p27 exclusively during G1...
  38. ncbi Ubiquitination of cyclin-dependent kinase inhibitor, Xic1, is mediated by the Xenopus F-box protein xSkp2
    Horng Ru Lin
    Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245 3207, USA
    Cell Cycle 5:304-14. 2006
    ..These studies provide the first characterization of the SCF in Xenopus and its role in the ubiquitination of CDK inhibitor, Xic1, during DNA replication initiation...
  39. ncbi Antimitogenesis linked to regulation of Skp2 gene expression
    Sheryl A Stewart
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    J Biol Chem 279:29109-13. 2004
    ..Our data show that inhibition of F-box protein gene expression can underlie the effect of a potent antimitogen...
  40. 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
    ....
  41. ncbi Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression, possibly via p27 proteolysis
    Taka aki Masuda
    Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu 874 0838, Japan
    Cancer Res 62:3819-25. 2002
    ..Skp2 can play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinoma as well as a strong prognostic marker...
  42. pmc Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer
    Sabina Signoretti
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 110:633-41. 2002
    ..We conclude that Skp2 has oncogenic potential in breast epithelial cells and is overexpressed in a subset of breast carcinomas (ER- and Her-2 negative) for which Skp2 inhibitors may represent a valid therapeutic option...
  43. ncbi Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase
    T Kamura
    Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Science 284:657-61. 1999
    ..These findings provide a further link between VHL and the cellular ubiquitination machinery...
  44. pmc Essential role of Skp2-mediated p27 degradation in growth and adaptive expansion of pancreatic beta cells
    Lingwen Zhong
    Larry Hillblom Islet Research Center and Molecular Biology Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
    J Clin Invest 117:2869-76. 2007
    ..These results indicate that the Skp2-mediated degradation pathway regulating the cellular degradation of p27 is essential for establishing beta cell mass and to respond to increased metabolic demand associated with insulin resistance...
  45. ncbi Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer
    Susanne Radke
    Department of Medicine, Division of Hematology Oncology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Oncogene 24:3448-58. 2005
    ..These findings therefore suggest that Skp2B overexpression is also observed in breast cancers and identify Skp2B as a putative oncogene...
  46. ncbi Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors
    Jia Qing Li
    Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 2733, USA
    Int J Oncol 25:87-95. 2004
    ..Thus, overexpression of Skp2 is associated with colorectal carcinogenesis and late metastasis to lymph nodes, whereas relative reduction of Skp2 is correlated with local invasion of primary carcinoma...
  47. ncbi Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation
    Mark Bond
    Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK
    Cardiovasc Res 69:198-206. 2006
    ..Here we investigate the mechanisms regulating p21Cip1 levels in VSMCs and its role in controlling VSMC proliferation...
  48. ncbi Relationship between levels of Skp2 and P27 in breast carcinomas and possible role of Skp2 as targeted therapy
    Wei Qiang Zheng
    Department of Pathology, Changhai Hospital, Second Military Medical University, 174 Chang Hai Road, Shanghai 200433, China
    Steroids 70:770-4. 2005
    ..Thus far, there is no specific therapy for the ER-negative and HER-2/neu resistant groups, which are among the subset of aggressive tumors...
  49. ncbi Focal adhesion kinase (FAK)-dependent regulation of S-phase kinase-associated protein-2 (Skp-2) stability. A novel mechanism regulating smooth muscle cell proliferation
    Mark Bond
    Bristol Heart Institute, University of Bristol, Bristol BS2 8HW, United Kingdom
    J Biol Chem 279:37304-10. 2004
    ..Taken together, these data demonstrate that the vascular ECM controls SMC proliferation via FAK-dependent regulation of Skp-2 protein stability...
  50. pmc Amplification and overexpression of SKP2 are associated with metastasis of non-small-cell lung cancers to lymph nodes
    Sana Yokoi
    Department of Molecular Cytogenetics, Graduate School of Biomedical Science, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Am J Pathol 165:175-80. 2004
    ..Our results suggest that SKP2 may be involved in progression of NSCLC, and that targeting this molecule could represent a promising therapeutic option...
  51. pmc Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation
    Haojie Huang
    Department of Biochemistry, and Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 102:1649-54. 2005
    ..Furthermore, expression of the FOXO1 protein is lost in a mouse lymphoma model, where Skp2 is overexpressed. These data suggest that the Skp2-promoted proteolysis of FOXO1 plays a key role in tumorigenesis...
  52. ncbi Expression of Skp2, a p27(Kip1) ubiquitin ligase, in malignant lymphoma: correlation with p27(Kip1) and proliferation index
    Megan S Lim
    Department of Pathology and ARUP Institute for Clinical and Experimental Pathology, University of Utah, Salt Lake City, UT 84132
    Blood 100:2950-6. 2002
    ..The absence of this relationship in aggressive lymphomas suggests that other factors contribute to deregulation of p27(Kip1) expression in these tumors...
  53. pmc Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions
    Han Liu
    Molecular Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 21:2385-98. 2007
    ..Our data conclude an essential post-translational regulation of MLL by the cell cycle ubiquitin/proteasome system (UPS) assures the temporal necessity of MLL in coordinating cell cycle progression...
  54. ncbi Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate
    Eun Hee Shim
    Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cancer Res 63:1583-8. 2003
    ..Our data suggest that SKP2 acts as an oncoprotein in the mouse prostate gland, probably through its function as a limiting factor for ubiquitin-dependent degradation of p27...
  55. ncbi Inhibition of cell proliferation of Tenon's capsule fibroblast by S-phase kinase-interacting protein 2 targeting SiRNA through increasing p27 protein level
    Feng Wang
    Department of Ophthalmology, First Clinical College, Harbin Medical University, Harbin, China
    Invest Ophthalmol Vis Sci 51:1475-82. 2010
    ..In the present study, the authors investigated whether small interfering RNA (siRNA)-mediated gene silencing of Skp2 can be used to increase p27(kip1) level and inhibit cell proliferation in rabbit Tenon's capsule fibroblast (rTF)...
  56. ncbi Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases
    P Zhou
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 2:571-80. 1998
    ..The finding that the F box-containing SCF components are unstable suggests a mechanism of regulating SCF function through ubiquitination and proteolysis of F box components...
  57. pmc A novel target gene, SKP2, within the 5p13 amplicon that is frequently detected in small cell lung cancers
    Sana Yokoi
    Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
    Am J Pathol 161:207-16. 2002
    ..Our results indicate that SKP2 is likely to be a target of the 5p13 amplification and to play an important role in the growth of SCLC cells...
  58. ncbi The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma
    Ma anit Shapira
    Department of Surgery, Rambam Medical Center and the Technion Israel Institute of Technology, Haifa, Israel
    Cancer 103:1336-46. 2005
    ..The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma...
  59. ncbi Regulation of the cell cycle by SCF-type ubiquitin ligases
    Keiichi I Nakayama
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    Semin Cell Dev Biol 16:323-33. 2005
    ..Clinical evidence also suggests that dysregulation of these F-box proteins contributes to human cancers...
  60. ncbi The expression of the F-box protein Skp2 is negatively associated with p27 expression in human pituitary tumors
    Madalina Musat
    Department of Endocrinology, St Bartholomew s Hospital, London EC1A 7BE, UK
    Pituitary 5:235-42. 2002
    ..Our data suggest that increased p27 degradation through the ubiquitin-proteasome pathway could be regulated in pituitary tumors by changes in Skp2 expression, although other factors probably also play a role...
  61. ncbi Skp2-mediated degradation of p27 regulates progression into mitosis
    Keiko Nakayama
    National Institute of Advanced Industrial Science and Technology AIST, Biological Information Research Center, Tokyo 135 0064, Japan
    Dev Cell 6:661-72. 2004
    ..These data suggest that p27 proteolysis is necessary for the activation of not only Cdk2 but also Cdc2, and that Skp2 contributes to regulation of G(2)-M progression by mediating the degradation of p27...
  62. pmc p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2
    Geneviève Rodier
    Institut de recherche en immunovirologie et cancérologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
    J Cell Biol 168:55-66. 2005
    ..We propose that p107, in addition to its interaction with E2F, inhibits cell proliferation through the control of Skp2 expression and the resulting stabilization of p27...
  63. ncbi Control of DNA synthesis and mitosis by the Skp2-p27-Cdk1/2 axis
    Michele Pagano
    Department of Pathology, New York University School of Medicine and NYU Cancer Institute, 550 First Avenue, MSB 599, New York, NY 10016, USA
    Mol Cell 14:414-6. 2004
    ....
  64. pmc Role of Cks1 overexpression in oral squamous cell carcinomas: cooperation with Skp2 in promoting p27 degradation
    Shojiro Kitajima
    Department of Oral Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami Ku, Hiroshima 734 8553, Japan
    Am J Pathol 165:2147-55. 2004
    ..These findings suggest that Cks1 overexpression may play an important role for OSCC development through Skp2-mediated p27 degradation, and that Cks1 siRNA can be a novel modality of gene therapy...
  65. pmc Myc degradation: dancing with ubiquitin ligases
    Bruno Amati
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Proc Natl Acad Sci U S A 101:8843-4. 2004
  66. ncbi Rho GTPase, Rac1, regulates Skp2 levels, vascular smooth muscle cell proliferation, and intima formation in vitro and in vivo
    Mark Bond
    Bristol Heart Institute, University of Bristol, Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK
    Cardiovasc Res 80:290-8. 2008
    ..We investigated the role of Rac(1) in the regulation of Skp2 in rat VSMC...
  67. ncbi An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant
    Peng Ji
    Department of Developmental and Molecular Biology, The Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Mol Cell 16:47-58. 2004
    ..These results identify an Rb-Skp2-p27 pathway in Rb function, which may be involved in inhibition of tumor progression...
  68. ncbi Immunohistochemical study of Skp2 and Jab1, two key molecules in the degradation of P27, in lung adenocarcinoma
    Akiteru Goto
    Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Pathol Int 54:675-81. 2004
    ..Thus, Skp2 and Jab1 regulate P27 degradation, and might contribute to the development and progression of lung AD through P27-mediated and -unmediated mechanisms...
  69. ncbi A license to kill: transcriptional activation and enhanced turnover of Myc by the SCF(kp2) ubiquitin ligase
    Jianping Jin
    Cancer Cell 3:517-8. 2003
    ....
  70. ncbi Three different binding sites of Cks1 are required for p27-ubiquitin ligation
    Danielle Sitry
    Unit of Biochemistry, The B Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    J Biol Chem 277:42233-40. 2002
    ..The interaction of Skp2 with the substrate is further strengthened by the association of the Cdk-binding site of Cks1 with Cdk2/cyclin E, to which phosphorylated p27 is bound...
  71. ncbi A splice variant of Skp2 is retained in the cytoplasm and fails to direct cyclin D1 ubiquitination in the uterine cancer cell line SK-UT
    S Ganiatsas
    Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, St-Andrew's Place, East Melbourne, Melbourne, Victoria, 3002, Australia
    Oncogene 20:3641-50. 2001
    ..Finally, our data indicates that differential splicing of F-box proteins may represent an additional level of regulation of the F-box mediated ubiquitination pathway...
  72. pmc Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34
    J H Seol
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Genes Dev 13:1614-26. 1999
    ..We conclude that Cdc53/Hrt1 comprise a highly conserved module that serves as the functional core of a broad variety of heteromeric ubiquitin ligases...
  73. ncbi Prognostic role of p27Kip1 deregulation in colorectal cancer
    Dan D Hershko
    Department of Surgery, Rambam Medical Center, Haifa, Israel
    Cancer 107:668-75. 2006
    ....
  74. ncbi Involvement of p27(KIP1) degradation by Skp2 in the regulation of proliferation in response to wounding of corneal epithelium
    Kazuhiko Yoshida
    Department of Ophthalmology, Hokkaido University School of Medicine, Sapporo, Japan
    Invest Ophthalmol Vis Sci 43:364-70. 2002
    ..To examine the expression of the p27(KIP1)in the normal and epithelial-scraped cornea and whether degradation of p27(KIP1)by Skp2 is involved in the regulation of cell proliferation in response to wounding of the corneal epithelium...
  75. ncbi Significance of skp2 expression in primary breast cancer
    Hideto Sonoda
    Department of Surgery, Kyushu University Hospital at Beppu, Beppu, Japan
    Clin Cancer Res 12:1215-20. 2006
    ..We herein examined the Skp2 expression in breast cancer and attempted to identify any associations between the Skp2 expression status and either the clinicopathologic variables or the patient's prognosis...
  76. ncbi Skp2 overexpression is highly representative of intrinsic biological aggressiveness and independently associated with poor prognosis in primary localized myxofibrosarcomas
    Hsuan Ying Huang
    Departments of Pathology and Radiation Oncology and Graduate institute of Clinical Medical Science, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University, 123 Ta Pei Road, Niao Sung, Kaohsiung County, Taiwan
    Clin Cancer Res 12:487-98. 2006
    ..We analyzed the prognostic utility of p27(Kip1) and its interacting cell cycle regulators in myxofibrosarcomas...
  77. ncbi SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells
    Sabyasachi Bhattacharya
    Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140, USA
    Oncogene 22:2443-51. 2003
    ..We conclude that p130 is a substrate of the SCF(SKP2) ubiquitin ligase and this E3 ligase regulates p130 abundance during the cell cycle...
  78. ncbi S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications
    Youyi Dong
    Department of Physiology, Kagawa Medical University, Kagawa 761 0793, Japan
    Oncol Rep 10:321-5. 2003
    ..These findings indicated that Skp2 expression was closely associated with tumor progression and represented an independent marker for prognosis of LSCC...
  79. ncbi Down-regulation of SKP2 induces apoptosis in lung-cancer cells
    Sana Yokoi
    Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo ku, Tokyo 113 8510, Japan
    Cancer Sci 94:344-9. 2003
    ....
  80. ncbi Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit
    Ulrich K Binné
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts, MA 02129, USA
    Nat Cell Biol 9:225-32. 2007
    ..The results reveal an unexpected physical convergence between the pRB tumour-suppressor protein and E3 ligase complexes, and raise the possibility that pRB may direct APC/C to additional targets during pRB-mediated cell-cycle exit...
  81. ncbi Cooperative organization in a macromolecular complex
    Markus A Seeliger
    MRC Centre for Protein Engineering, Hills Road, Cambridge CB2 2QH, UK
    Nat Struct Biol 10:718-24. 2003
    ..Simultaneous and synergistic binding of multiple subunits in a complex provides the specificity and control required before the key cell-cycle regulator p27 is committed to degradation...
  82. ncbi Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation
    A Marti
    Friedrich Miescher Institut, Basel, Switzerland
    Nat Cell Biol 1:14-9. 1999
    ....
  83. ncbi GATA-2/estrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21(WAF1) and p27(Kip1) proteins
    Sachiko Ezoe
    Department of Hematology Oncology and Molecular Oncology, Osaka University Graduate School of Medicine, 2 2, Yamada oka, Suita, Osaka, Japan
    Blood 100:3512-20. 2002
    ..These results suggest that GATA-2 may regulate expression levels of p21(WAF1) and p27(Kip1), thereby contributing to the quiescence of hematopoietic stem/progenitor cells...
  84. ncbi Phosphoinositide-3-kinase signaling controls S-phase kinase-associated protein 2 transcription via E2F1 in pancreatic ductal adenocarcinoma cells
    Maximilian Reichert
    Department of Internal Medicine, Technical University of Munich, Munich, Germany
    Cancer Res 67:4149-56. 2007
    ..The complex and profound connection of PI3K/AKT1 signaling to the cell cycle qualifies this pathway as a suitable target for therapeutic intervention in PDAC...
  85. ncbi A second RING to destroy p27(Kip1)
    Ludger Hengst
    Nat Cell Biol 6:1153-5. 2004
  86. ncbi Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases
    Bing Hao
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 26:131-43. 2007
    ....
  87. pmc Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis
    Hideo Nishitani
    Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Higashi ku, Fukuoka, Japan
    EMBO J 25:1126-36. 2006
    ..PCNA is essential for Cul4- but not Skp2-directed degradation during DNA replication and following ultraviolet-irradiation. Our data unravel multiple distinct pathways regulating Cdt1 to block re-replication...
  88. ncbi Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries
    Florian Blaschke
    Division of Endocrinology, Diabetes, and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, USA
    Circ Res 95:e110-23. 2004
    ..The full text of this article is available online at http://circres.ahajournals.org...
  89. pmc DDB1 maintains genome integrity through regulation of Cdt1
    Courtney A Lovejoy
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
    Mol Cell Biol 26:7977-90. 2006
    ..Therefore, DDB1 prevents DNA lesions from accumulating in replicating human cells, in part by regulating Cdt1 degradation...
  90. ncbi Oncogenic Ras blocks transforming growth factor-beta-induced cell-cycle arrest by degradation of p27 through a MEK/Erk/SKP2-dependent pathway
    Hein Schepers
    Division of Hematology, Department of Medicine, University Medical Center Groningen, The Netherlands
    Exp Hematol 33:747-57. 2005
    ....
  91. ncbi Ubiquitination of p27Kip1 requires physical interaction with cyclin E and probable phosphate recognition by SKP2
    Dana Ungermannova
    Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA
    J Biol Chem 280:30301-9. 2005
    ..Thus, our data unravel the molecular organization of the ubiquitination complex that catalyzes p27 ubiquitination and provide unique insights into the specificity of substrate recognition by SCF(Skp2)...
  92. pmc Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27 Kip1 degradation
    Leonor M Sarmento
    Center of Regenerative Medicine and Technology, Massachusetts General Hospital, Boston, MA, USA
    J Exp Med 202:157-68. 2005
    ....
  93. ncbi Retinoic acid stabilizes p27Kip1 in EBV-immortalized lymphoblastoid B cell lines through enhanced proteasome-dependent degradation of the p45Skp2 and Cks1 proteins
    Paola Zancai
    Immunovirology and Biotherapy Unit, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano, PN, Italy
    Oncogene 24:2483-94. 2005
    ....
  94. pmc SCFSkp2 complex targeted by Epstein-Barr virus essential nuclear antigen
    Jason S Knight
    Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
    Mol Cell Biol 25:1749-63. 2005
    ....
  95. ncbi Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm
    Eddy S Yang
    Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33136, USA
    J Biol Chem 278:46862-8. 2003
    ..These data suggest that Cdk2 mislocalization is central to the antiproliferative effects of 1,25-(OH)2D3...
  96. ncbi CD28 costimulation mediates transcription of SKP2 and CKS1, the substrate recognition components of SCFSkp2 ubiquitin ligase that leads p27kip1 to degradation
    Leonard J Appleman
    Department of Medical Oncology, Dana Farber Cancer Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Cell Cycle 5:2123-9. 2006
    ..Thus, in primary T lymphocytes CD28 costimulation can directly regulate cell cycle progression by inducing transcription of the substrate recognition components of SCF(skp2) ubiquitin ligase that targets p27(kip1) for degradation...
  97. ncbi Down-regulation of Skp2 is correlated with p27-associated cell cycle arrest induced by phenylacetate in human prostate cancer cells
    Takuji Shibahara
    Department of Urology, Mie University Facutly of Medicine, Tsu, Mie, Japan
    Anticancer Res 25:1881-8. 2005
    ..Therapeutic strategies designed to reduce Skp2 may clinically play an important role in the treatment of both androgen-sensitive and hormone-refractory prostate cancer...
  98. ncbi FBW2 targets GCMa to the ubiquitin-proteasome degradation system
    Chih Sheng Yang
    Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan
    J Biol Chem 280:10083-90. 2005
    ..Our study identifies the SCF(hFBW2) E3 complex as the key machinery that targets hGCMa to the ubiquitin-proteasome degradation system...
  99. pmc Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer
    David Frescas
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Nat Rev Cancer 8:438-49. 2008
    ....
  100. pmc Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1
    P Kaiser
    The Scripps Research Institute TSRI, La Jolla, California 92037 USA
    Genes Dev 12:2587-97. 1998
    ..Our data, in combination with previously published results, also provide evidence for distinct SCF complexes in vivo and support the idea that their F-box subunits mediate SCF substrate specificity...
  101. pmc CDK9 is constitutively expressed throughout the cell cycle, and its steady-state expression is independent of SKP2
    Judit Garriga
    Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140, USA
    Mol Cell Biol 23:5165-73. 2003
    ..Therefore, the SCF(SKP2) ubiquitin ligase does not regulate CDK9 expression in a cell cycle-dependent manner...

Research Grants29

  1. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  2. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer. ..
  3. Physiologic Regulation of Hematopoiesis by Notch
    Nadia Carlesso; Fiscal Year: 2011
    ..The long term goal of this project is to evaluate the role of the Notch signaling pathway both in normal bone marrow reconstitution and in leukemias and to identify novel targets of therapeutic intervention. ..
  4. Regulation and Role of Ornithine Decarboxylase in Cell Proliferation and Cancer
    John L Cleveland; Fiscal Year: 2013
    ..abstract_text> ..
  5. B-RAF Regulation of the Cell Cycle in Melanoma
    Andrew E Aplin; Fiscal Year: 2013
    ..At the completion of our experiments, we aim to have identified new targets for therapeutic intervention to prevent aberrant melanoma cell proliferation. ..
  6. Plk1 in Chemo-resistance of Cancer
    Xiaoqi Liu; Fiscal Year: 2013
    ..If successful, the predicted results will identify Plk1 as a novel target, inhibition of which will prevent chemoresistance, thus increasing the efficacy of chemotherapy. ..
  7. Controlling VSMC Proliferation and Migration
    Ming Hui Zou; Fiscal Year: 2013
    ....
  8. The crosstalk between the PI3K/Akt signal and Skp2 in prostate cancer progression
    Hui Kuan Lin; Fiscal Year: 2013
    ..Understanding the important role of Skp2 and Skp2 S72 phopshorylation in prostate cancer progression and metastasis may provide an important therapeutic implication for human prostate cancers. ..
  9. ANDROGEN RECEPTOR REGULATION OF REPRODUCTIVE FUNCTION
    Elizabeth M Wilson; Fiscal Year: 2010
    ..Our studies will provide insight into mechanisms whereby AR regulates gene transcription in human cells. ..
  10. Mechanisms of p27Kipl Proteolysis in Cancer Cells
    Xuedong Liu; Fiscal Year: 2012
    ..Our studies could lead to novel therapy for malignant cancers and improve prognosis of patient with aggressive tumors. ..
  11. MEIOTIC CELL CYCLE REGULATION IN REPRODUCTION
    Stuart Ravnik; Fiscal Year: 2002
    ..CycAl, Cdkl, and Cdk2 expression will be determined using immunohistochemistry. Co-immunoprecipitated proteins will be examined as Aim 1. ..
  12. ECM MATRIX, PROTEASE AND MELANOMA PROLIFERATION
    Yves DeClerck; Fiscal Year: 2007
    ..This information will lead to a better understanding of the role of matrix degrading proteases such as MMPs in cancer, which will be important in the design of better clinical trials involving MMP inhibitors in cancer therapy. ..
  13. MECHANISMS OF CELL CYCLE CONTROL DURING MAMMARY GLAND DE
    Hui Zhang; Fiscal Year: 2001
    ..These studies should also provide a basis to design novel strategies for diagnosis, prognosis, and therapeutic treatment of breast cancers. ..
  14. Regulation of Bladder Smooth Muscle Hyperplasia
    Paul Austin; Fiscal Year: 2007
    ..Work of this nature may decrease the morbidity and mortality that is caused by bladder outlet obstruction. ..
  15. Nedd8 Regulation of Ubiquitin E3 Ligases in Adipocytes
    RON MORRISON; Fiscal Year: 2006
    ..We predict that pathways responsible for adding and removing Nedd8 are essential for SCF E3 ligase activity, p27 ubiquitylation and degradation, and adipocyte hyperplasia. ..
  16. PROTEOLYSIS AND MAMMALIAN GL/S CELL CYCLE TRANSITION
    Hui Zhang; Fiscal Year: 2003
    ..These studies will also provide a molecular basis for designing novel strategies for the diagnostic and therapeutic treatment of human cancer. ..
  17. Structural biology of SCFs and related ubiquitin Ligases
    Nikola Pavletich; Fiscal Year: 2005
    ..They will also help address whether E3s, many of which are implicated in diseases such as cancer, are likely targets for drug discovery. ..
  18. Optimized High-Throughput Screen for Small Molecule Inhibitors of P27 Degradation
    Dieter Wolf; Fiscal Year: 2007
    ..If validated, the assay will be used to perform a SMIP screen at the San Diego Center for Chemical Genomics, one of the Molecular Library Screening Centers in the NIH Roadmap Network. [unreadable] [unreadable] [unreadable]..
  19. Role of Skp2 and Skp2B in breast cancer
    Doris Germain; Fiscal Year: 2009
    ..abstract_text> ..
  20. THE S. CEREVISIAE S PHASE CHECKPOINT
    Steven Reed; Fiscal Year: 2003
    ....
  21. Mechanism of Notch Transcriptional Activation
    Katherine Jones; Fiscal Year: 2006
    ..These studies will help elucidate the Notch transactivation mechanism and its role in the modification and destruction of the ICD, and may suggest approaches for blocking Notch signaling in human cancers. ..
  22. Genistein induces thymic atrophy: a health concern?
    Paul Cooke; Fiscal Year: 2006
    ..These studies will advance our understanding of isoflavone effects on the immune system, and also may have relevance for soy-fed infants and laboratory rodents consuming soy-based feed. ..
  23. Cell Cycle Control by Rho GTPases and Their Effectors
    RICHARD ASSOIAN; Fiscal Year: 2006
    ....
  24. Cell cycle control of vascular remodeling
    RICHARD ASSOIAN; Fiscal Year: 2009
    ..This research will help to identify the genes and proteins that regulate smooth muscle cell proliferation. It will also test the importance of these molecules in an in vivo model of vascular injury. ..
  25. The role of Cyclin E in growth control and tumorogenesis
    Steven Reed; Fiscal Year: 2008
    ..It is hoped that insights gained from understanding these fundamental mechanisms of oncogenesis will lead to new approaches to cancer prevention and therapy. ..
  26. CYCLIN D1 AND CELL ADHESION
    RICHARD ASSOIAN; Fiscal Year: 2007
    ..abstract_text> ..
  27. Role of P80 pro-IL-16 in T Cell Malignancy
    Yujun Zhang; Fiscal Year: 2008
    ..This study will lead to a considerable insight of the role of p80 pro-IL-16 in the T cell cycle regulation and T cell malignancy and help to identify diagnostic and/or therapeutical targets for human T cell malignancies. ..