Cdk4

Summary

Gene Symbol: Cdk4
Description: cyclin dependent kinase 4
Alias: CMM3, PSK-J3, cyclin-dependent kinase 4, cell division protein kinase 4
Species: human
Products:     Cdk4

Top Publications

  1. Kitagawa M, Higashi H, Jung H, Suzuki Takahashi I, Ikeda M, Tamai K, et al. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996;15:7060-9 pubmed
    Cyclin D-Cdk4/6 and cyclin A/E-Cdk2 are suggested to be involved in phosphorylation of the retinoblastoma protein (pRB) during the G1/S transition of the cell cycle...
  2. Nadal A, Jares P, Pinyol M, Conde L, Romeu C, Fernandez P, et al. Association of CDK4 and CCND1 mRNA overexpression in laryngeal squamous cell carcinomas occurs without CDK4 amplification. Virchows Arch. 2007;450:161-7 pubmed
    b>CDK4 is involved in the control of G1-S phase transition as a part of the CCND1/CDK4 complexes. CCNDI and CDK4 gene alterations have been implicated in the development of different tumors...
  3. Goldstein A, Chan M, Harland M, Gillanders E, Hayward N, Avril M, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66:9818-28 pubmed
    ..high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM)...
  4. Poomsawat S, Buajeeb W, Khovidhunkit S, Punyasingh J. Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions. J Oral Pathol Med. 2010;39:793-9 pubmed publisher
    b>Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC)...
  5. Molven A, Grimstvedt M, Steine S, Harland M, Avril M, Hayward N, et al. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes Chromosomes Cancer. 2005;44:10-8 pubmed
    ..Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide...
  6. Italiano A, Bianchini L, Gjernes E, Keslair F, Ranchere Vince D, Dumollard J, et al. Clinical and biological significance of CDK4 amplification in well-differentiated and dedifferentiated liposarcomas. Clin Cancer Res. 2009;15:5696-703 pubmed publisher
    ..HMGA2 genes are consistently amplified in well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) whereas CDK4 is frequently but not always amplified in these tumors...
  7. Coleman K, Wautlet B, Morrissey D, Mulheron J, Sedman S, Brinkley P, et al. Identification of CDK4 sequences involved in cyclin D1 and p16 binding. J Biol Chem. 1997;272:18869-74 pubmed
    Activation of CDK4 is regulated, in part, by its association with a D-type cyclin. Conversely, CDK4 activity is inhibited when it is bound to the cyclin-dependent kinase inhibitor, p16(INK4A)...
  8. LaBaer J, Garrett M, Stevenson L, Slingerland J, Sandhu C, Chou H, et al. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997;11:847-62 pubmed
    The association of cdk4 with D-type cyclins to form functional kinase complexes is comparatively inefficient. This has led to the suggestion that assembly might be a regulated step...
  9. Lindberg D, Hessman O, Akerstrom G, Westin G. Cyclin-dependent kinase 4 (CDK4) expression in pancreatic endocrine tumors. Neuroendocrinology. 2007;86:112-8 pubmed
    ..b>CDK4 is central to the cell cycle control in pancreatic beta cells, and we have assessed whether CDK4 expression is ..

More Information

Publications75

  1. Braden W, McClendon A, Knudsen E. Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly. Oncogene. 2008;27:7083-93 pubmed publisher
    ..Although the role of CDK2 activity on the replication apparatus has been extensively studied, the role of CDK4/6 in DNA replication control is less understood...
  2. Rocha A, Paternot S, Coulonval K, Dumont J, Soares P, Roger P. Cyclic AMP inhibits the proliferation of thyroid carcinoma cell lines through regulation of CDK4 phosphorylation. Mol Biol Cell. 2008;19:4814-25 pubmed publisher
    ..However, cAMP differentially inhibited the pRb-kinase activity and T172-phosphorylation of CDK4 complexed to cyclin D1 or cyclin D3, whereas CDK-activating kinase activity remained unaffected...
  3. Ye Y, Yang H, Grossman H, Dinney C, Wu X, Gu J. Genetic variants in cell cycle control pathway confer susceptibility to bladder cancer. Cancer. 2008;112:2467-74 pubmed publisher
    ..of 10 potential functional single nucleotide polymorphisms (SNPs) from 7 cell cycle control genes, P53, P21, P27, CDK4, CDK6, CCND1, and STK15, were evaluated on bladder cancer risk in a case-control study of 696 bladder cancer cases ..
  4. Hirai H, Roussel M, Kato J, Ashmun R, Sherr C. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol Cell Biol. 1995;15:2672-81 pubmed
    ..Two novel members of the mouse INK4 gene family, p19 and p18, that specifically inhibit the kinase activities of CDK4 and CDK6, but do not affect those of cyclin E-CDK2, cyclin A-CDK2, or cyclin B-CDC2, were isolated...
  5. Retzer Lidl M, Schmid R, Schneider G. Inhibition of CDK4 impairs proliferation of pancreatic cancer cells and sensitizes towards TRAIL-induced apoptosis via downregulation of survivin. Int J Cancer. 2007;121:66-75 pubmed
    ..Abnormal regulation of the cell cycle is a hallmark of neoplasia. Cyclin-dependent kinase 4 (CDK4), a key regulator of G1-phase of the cell cycle, has been shown to be overexpressed in pancreatic cancer...
  6. Kato J, Matsuoka M, Strom D, Sherr C. Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol. 1994;14:2713-21 pubmed
    ..assembled holoenzymes composed of regulatory D-type cyclins and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting for progression through the G1 phase of the cell cycle in mammalian fibroblasts...
  7. Molenaar J, Ebus M, Koster J, van Sluis P, van Noesel C, Versteeg R, et al. Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma. Cancer Res. 2008;68:2599-609 pubmed publisher
    Genomic aberrations of Cyclin D1 (CCND1), CDK4, and CDK6 in neuroblastoma indicate that dysregulation of the G(1) entry checkpoint is an important cell cycle aberration in this pediatric tumor...
  8. LARREA M, Liang J, Da Silva T, Hong F, Shao S, Han K, et al. Phosphorylation of p27Kip1 regulates assembly and activation of cyclin D1-Cdk4. Mol Cell Biol. 2008;28:6462-72 pubmed publisher
    p27 mediates Cdk2 inhibition and is also found in cyclin D1-Cdk4 complexes...
  9. Bockstaele L, Kooken H, Libert F, Paternot S, Dumont J, De Launoit Y, et al. Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors". Mol Cell Biol. 2006;26:5070-85 pubmed
    Cyclin-dependent kinase 4 (CDK4) is a master integrator of mitogenic and antimitogenic extracellular signals. It is also crucial for many oncogenic transformation processes...
  10. Yu Q, Sicinska E, Geng Y, Ahnström M, Zagozdzon A, Kong Y, et al. Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006;9:23-32 pubmed
    ..We report that the ability of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role for cyclin D1 in breast cancer formation...
  11. Larochelle S, Batliner J, Gamble M, Barboza N, Kraybill B, Blethrow J, et al. Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics. Nat Struct Mol Biol. 2006;13:55-62 pubmed
    ..Thus, Cdk7 accomplishes dual functions in cell-cycle control and transcription not through promiscuity but through distinct, stringent modes of substrate recognition. ..
  12. Michaud K, Solomon D, Oermann E, Kim J, Zhong W, Prados M, et al. Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. Cancer Res. 2010;70:3228-38 pubmed publisher
    Activation of cyclin-dependent kinases 4 and 6 (cdk4/6) occurs in the majority of glioblastoma multiforme (GBM) tumors, and represents a promising molecular target for the development of small molecule inhibitors...
  13. Kehn K, Deng L, de La Fuente C, Strouss K, Wu K, Maddukuri A, et al. The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells. Retrovirology. 2004;1:6 pubmed
    ..Immunoprecipitations from HTLV-1 infected cells showed p21/waf1 in a stable complex with cyclin D2/cdk4. This complex is active as it phosphorylates the Rb protein in kinase assays...
  14. Miliani de Marval P, Macias E, Conti C, Rodriguez Puebla M. Enhanced malignant tumorigenesis in Cdk4 transgenic mice. Oncogene. 2004;23:1863-73 pubmed
    In a previous study, we reported that overexpression of cyclin-dependent kinase-4 (CDK4) in mouse epidermis results in epidermal hyperplasia, hypertrophy and severe dermal fibrosis...
  15. Aggarwal P, Vaites L, Kim J, Mellert H, Gurung B, Nakagawa H, et al. Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell. 2010;18:329-40 pubmed publisher
    ..The current work reveals a molecular relationship between cyclin D1/CDK4 kinase and protein arginine methyltransferase 5 (PRMT5), an enzyme associated with histone methylation and ..
  16. Connell Crowley L, Harper J, Goodrich D. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell. 1997;8:287-301 pubmed
    ..In vitro phosphorylation by cyclin D1/Cdk4 leads to inactivation of pRb in a microinjection-based in vivo cell cycle assay...
  17. Chen J, Saha P, Kornbluth S, Dynlacht B, Dutta A. Cyclin-binding motifs are essential for the function of p21CIP1. Mol Cell Biol. 1996;16:4673-82 pubmed
    ..recognizes the Cy1 site of p21 specifically disrupts the association of p21 with cyclin E-Cdk2 and with cyclin D1-Cdk4 in cell extracts...
  18. Vlach J, Hennecke S, Amati B. Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J. 1997;16:5334-44 pubmed
    ..We propose that cellular p27 must also exist transiently in a cyclin-bound non-inhibitory conformation in vivo. ..
  19. Kato J, Matsushime H, Hiebert S, Ewen M, Sherr C. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993;7:331-42 pubmed
    ..Complexes of the cyclin-dependent kinase, cdk4, and each of three different D-type cyclins, assembled in insect Sf9 cells, phosphorylated a pRb fusion protein in ..
  20. Soufir N, Avril M, Chompret A, Demenais F, Bombled J, Spatz A, et al. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet. 1998;7:209-16 pubmed
    Germline mutations in the p16 and CDK4 genes have been reported in a subset of melanoma pedigrees, but their prevalence is not well known...
  21. Lin J, Jinno S, Okayama H. Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence. Oncogene. 2001;20:2000-9 pubmed
    ..start, yet many mesenchymal cells express three seemingly redundant D cyclins and similarly, seemingly redundant Cdk4 and Cdk6 as their kinase partners...
  22. Kumar R, Smeds J, Berggren P, Straume O, Rozell B, Akslen L, et al. A single nucleotide polymorphism in the 3'untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare. Int J Cancer. 2001;95:388-93 pubmed
    In this report we present the results of mutational analysis of the CDKN2B, CDKN2C, CDK4, p53 genes and 5'UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/..
  23. Haller K, Wu Y, Derow E, Schmitt I, Jeang K, Grassmann R. Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein. Mol Cell Biol. 2002;22:3327-38 pubmed
    ..Tax stimulates the cell cycle in the G(1) phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6 holoenzyme complexes. Here we show that Tax directly interacts with CDK4...
  24. Serrano M, Hannon G, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366:704-7 pubmed
    ..The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase...
  25. Ray A, James M, Larochelle S, Fisher R, Blain S. p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes. Mol Cell Biol. 2009;29:986-99 pubmed publisher
    ..Although p27 associates with cyclin D-cyclin-dependent kinase 4 (cdk4) constitutively, whether or not it inhibits this complex is dependent on the absence or presence of a specific ..
  26. Pjanova D, Molven A, Akslen L, Engele L, Streinerte B, Azarjana K, et al. Identification of a CDK4 R24H mutation-positive melanoma family by analysis of early-onset melanoma patients in Latvia. Melanoma Res. 2009;19:119-22 pubmed publisher
    ..lt; or =40 years) Latvian melanoma patients for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. We observed no disease-related mutations in CDKN2A, but one patient had a CDK4 R24H mutation and strong family ..
  27. Schrage Y, Lam S, Jochemsen A, Cleton Jansen A, Taminiau A, Hogendoorn P, et al. Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro. J Cell Mol Med. 2009;13:2843-52 pubmed publisher
    ..The aim of this study is to investigate genes involved in cell cycle control: CDK4, CDKN2A/p16, cyclin D1, p21, p53, MDM2 and c-MYC, which may point towards new therapeutic strategies...
  28. Zuo L, Weger J, Yang Q, Goldstein A, Tucker M, Walker G, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996;12:97-9 pubmed
  29. Takaki T, Echalier A, Brown N, Hunt T, Endicott J, Noble M. The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc Natl Acad Sci U S A. 2009;106:4171-6 pubmed publisher
    Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, ..
  30. Sirvent N, Coindre J, Maire G, Hostein I, Keslair F, Guillou L, et al. Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol. 2007;31:1476-89 pubmed
    ..liposarcomas and dedifferentiated liposarcomas are characterized by the amplification of MDM2 and CDK4 genes...
  31. Zarkowska T, Mittnacht S. Differential phosphorylation of the retinoblastoma protein by G1/S cyclin-dependent kinases. J Biol Chem. 1997;272:12738-46 pubmed
    ..We show here that three candidate pRB-inactivating kinases, CDK4-cyclin D1, CDK2-cyclin E, and CDK2-cyclin A, phosphorylate pRB differentially, each on a subset of authentic pRB ..
  32. Bockstaele L, Bisteau X, Paternot S, Roger P. Differential regulation of cyclin-dependent kinase 4 (CDK4) and CDK6, evidence that CDK4 might not be activated by CDK7, and design of a CDK6 activating mutation. Mol Cell Biol. 2009;29:4188-200 pubmed publisher
    The homologous cyclin-dependent kinases (CDK) CDK4 and CDK6 integrate mitogenic and oncogenic signaling cascades with the cell cycle...
  33. Lin D, Barbash O, Kumar K, Weber J, Harper J, Klein Szanto A, et al. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell. 2006;24:355-66 pubmed
    ..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1. ..
  34. Schachter M, Merrick K, Larochelle S, Hirschi A, Zhang C, Shokat K, et al. A Cdk7-Cdk4 T-loop phosphorylation cascade promotes G1 progression. Mol Cell. 2013;50:250-60 pubmed publisher
    ..It was unknown if Cdk7 also activates Cdk4 and Cdk6 to promote passage of the restriction (R) point, when continued cell-cycle progression becomes mitogen ..
  35. Diehl J, Sherr C. A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase. Mol Cell Biol. 1997;17:7362-74 pubmed
    ..cyclin subunit, mutation of this residue to alanine has profound effects on the behavior of the derived cyclin D1-CDK4 complexes...
  36. Lu J, Lin Y, Chang J, Yeh K, Chen R, Tsai J, et al. Clinical implications of deregulated CDK4 and Cyclin D1 expression in patients with human hepatocellular carcinoma. Med Oncol. 2013;30:379 pubmed publisher
    ..Overexpression of cell cycle regulators CDK4 and Cyclin D1 has been reported in many cancers...
  37. Zeng X, Shaikh F, Harrison M, Adon A, Trimboli A, Carroll K, et al. The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2. Oncogene. 2010;29:5103-12 pubmed publisher
    ..Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced CA, whereas silencing ..
  38. Wu A, Wu B, Guo J, Luo W, Wu D, Yang H, et al. Elevated expression of CDK4 in lung cancer. J Transl Med. 2011;9:38 pubmed publisher
    The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features...
  39. Yoshida A, Ushiku T, Motoi T, Shibata T, Beppu Y, Fukayama M, et al. Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics. Mod Pathol. 2010;23:1279-88 pubmed publisher
    ..behaviors, histological features, and genetic background (ie, amplified sequences of 12q13-15, including MDM2 and CDK4)...
  40. Pjanova D, Engele L, Randerson Moor J, Harland M, Bishop D, Newton Bishop J, et al. CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population. Melanoma Res. 2007;17:185-91 pubmed
    Germline mutations of the CDKN2A and CDK4 genes explain a significant proportion of familial melanoma. To date, there have been few published estimations of the prevalence of such mutations in sporadic melanoma patients...
  41. Xiang Z, Liang Z, Yanfeng H, Leitao K. Persistence of RSV promotes proliferation and epithelial-mesenchymal transition of bronchial epithelial cells through Nodal signaling. J Med Microbiol. 2017;66:1499-1505 pubmed publisher
    ..Moreover, Lefty and pSmad2/3 were assayed by Western blot and Cyclin D1, CDK4, c-myc and Bcl-2 induced by Nodal overepression or RSV infection were also assayed by real-time PCR...
  42. Wang J, Xu C, Wu H, Shen S. LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Braz J Med Biol Res. 2017;50:e6079 pubmed publisher
    ..The protein level of cell cycle progression-related molecules, including cyclin-dependent kinases (CDK4, CDK6), cyclin D1 (CCND1) and cell apoptosis-related molecule caspase 3 was detected by western blot...
  43. Chikenji A, Ando H, Nariyama M, Suga T, Iida R, Gomi K. MyoD is regulated by the miR-29a-Tet1 pathway in C2C12 myoblast cells. J Oral Sci. 2016;58:219-29 pubmed publisher
    ..myogenic regulatory factor 4 (Mrf4), muscle creatine kinase (Mck), and other cell cycle regulators such as Cdk4 and thymine DNA glycosylase (Tdg) cannot be explained in terms of the miR-29a-Tet1 pathway alone...
  44. Zheleva D, McInnes C, Gavine A, Zhelev N, Fischer P, Lane D. Highly potent p21(WAF1)-derived peptide inhibitors of CDK-mediated pRb phosphorylation: delineation and structural insight into their interactions with cyclin A. J Pept Res. 2002;60:257-70 pubmed
    ..Furthermore, it provides generic insights into molecular interactions governing cyclin groove recognition and lays the foundation for the development of peptidomimetic inhibitors of CDKs. ..
  45. Lee J, Ryu J, Han Y, Zia M, Kwon H, Noh H, et al. Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease. J Mol Cell Cardiol. 2016;97:169-79 pubmed publisher
    ..the expression of cell cycle-associated proteins, such as cyclin E, cyclin dependent kinase (CDK) 2, cyclin D1, and CDK4, via focal adhesion kinase and the phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt axis...
  46. Rossig L, Jadidi A, Urbich C, Badorff C, Zeiher A, Dimmeler S. Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells. Mol Cell Biol. 2001;21:5644-57 pubmed
    ..In addition, phosphorylation of p21(Cip1) at Thr 145 decreases the binding of the cyclin-dependent kinases Cdk2 and Cdk4 to p21(Cip1) and attenuates the Cdk2 inhibitory activity of p21(Cip1)...
  47. Bouillez A, Rajabi H, Pitroda S, Jin C, Alam M, Kharbanda A, et al. Inhibition of MUC1-C Suppresses MYC Expression and Attenuates Malignant Growth in KRAS Mutant Lung Adenocarcinomas. Cancer Res. 2016;76:1538-48 pubmed publisher
    ..the expression of key MYC target genes essential for the growth and survival of NSCLC cells, such as TERT and CDK4. Based on these results, we found that the combination of GO-203 and the BET bromodomain inhibitor JQ1, which ..
  48. Kangwan N, Kim Y, Han Y, Jeong M, Park J, Hahm K. Concerted actions of ameliorated colitis, aberrant crypt foci inhibition and 15-hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis-associated cancer. Int J Cancer. 2016;138:1482-93 pubmed publisher
    ..COX-2, STAT3 and NF-κB as well as significant ameliorations of β-catenin nuclear translocation, cyclin D1 and CDK4 were imposed with Shh inhibitors...
  49. Gyanchandani R, Kota K, Jonnalagadda A, Minteer T, Knapick B, Oesterreich S, et al. Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole. Oncotarget. 2017;8:66901-66911 pubmed publisher
    ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC...
  50. Hodgson A, Amemiya Y, Seth A, Djordjevic B, Parra Herran C. High-grade Müllerian Adenosarcoma: Genomic and Clinicopathologic Characterization of a Distinct Neoplasm With Prevalent TP53 Pathway Alterations and Aggressive Behavior. Am J Surg Pathol. 2017;41:1513-1522 pubmed publisher
    ..Copy number variations occurred at a mean of 28.8 per tumor; most frequently involved genes included CDK4, MDM2, GNAS, SGK1, and DICER1...
  51. van Ginkel J, de Leng W, de Bree R, van Es R, Willems S. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer. Oncotarget. 2016;7:61575-61586 pubmed publisher
    ..mutation rates of up to 83% in all tumors, compared to mutation rates of between 0 and 21% of CDKN2A, PIK3CA, HRAS, CDK4, FBXW7 and RB1...
  52. Sun C, Li S, Li D. Hsa-miR-134 suppresses non-small cell lung cancer (NSCLC) development through down-regulation of CCND1. Oncotarget. 2016;7:35960-35978 pubmed publisher
    ..by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1)...
  53. Juengel E, Thomas A, Rutz J, Makarevic J, Tsaur I, Nelson K, et al. Amygdalin inhibits the growth of renal cell carcinoma cells in vitro. Int J Mol Med. 2016;37:526-32 pubmed publisher
    ..Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by ..
  54. Wong D, Low I, Peverall J, Robbins P, Spagnolo D, Nairn R, et al. MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance. Pathology. 2016;48:203-9 pubmed publisher
    This study of 140 cases assessed the incidence of MDM2/CDK4 gene amplification in lipomatous neoplasms with histological features of a lipoma but which were of clinical concern due to large size (?50 mm) and/or deep-seated (subfascial) ..
  55. Lazaro J, Bailey P, Lassar A. Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation. Genes Dev. 2002;16:1792-805 pubmed
    Prior work has indicated that D-type cyclin-cdk4 complexes, which are only active in proliferating cells, can suppress the skeletal muscle differentiation program in proliferating myoblasts...
  56. Detjen K, Murphy D, Welzel M, Farwig K, Wiedenmann B, Rosewicz S. Downregulation of p21(waf/cip-1) mediates apoptosis of human hepatocellular carcinoma cells in response to interferon-gamma. Exp Cell Res. 2003;282:78-89 pubmed
    ..SK-Hep-1 cells revealed a deficient cyclin D induction in IFN-gamma-treated cells, resulting in reduced activity of CDK4 and CDK2 kinases and pRB hypophosphorylation. In contrast, apoptosis prevailed in IFN-gamma-treated HepG2 cultures...
  57. Wood A, Krytska K, Ryles H, Infarinato N, Sano R, Hansel T, et al. Dual ALK and CDK4/6 Inhibition Demonstrates Synergy against Neuroblastoma. Clin Cancer Res. 2017;23:2856-2868 pubmed publisher
    ..and ribociclib on in vitro proliferation, cell cycle, viability, caspase activation, and the cyclin D/CDK4/CDK6/RB and pALK signaling networks in cell lines with representative ALK status...
  58. Miller M, Molinelli E, Nair J, Sheikh T, Samy R, Jing X, et al. Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets. Sci Signal. 2013;6:ra85 pubmed publisher
    ..we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets...
  59. Elkahloun A, Krizman D, Wang Z, Hofmann T, Roe B, Meltzer P. Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers. Genomics. 1997;42:295-301 pubmed
    ..3, a region of DNA sequence amplification in human cancers. This cosmid, previously known to contain three genes (CDK4, SAS, and OS9), was sequenced, and that information was used for computer-assisted analysis...
  60. Orend G, Hunter T, Ruoslahti E. Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells. Oncogene. 1998;16:2575-83 pubmed publisher
  61. Zhang Y, Zhou Y, Liu Z, Fang W. [Cytoplasmic expression of CDK4 protein and its correlation with the clinicopathologic features and prognosis of lung cancer]. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32:1572-5 pubmed
    To evaluate the correlation of CDK4 protein expression in the cytoplasm with the clinicopathologic features and prognosis of lung cancer...
  62. Halder S, Beauchamp R, Datta P. Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res. 2005;307:231-46 pubmed
    ..Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1)...
  63. Deep G, Singh R, Agarwal C, Kroll D, Agarwal R. Silymarin and silibinin cause G1 and G2-M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: a comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene. 2006;25:1053-69 pubmed
    ..in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21...
  64. Vaughan C, Gohlke U, Sobott F, Good V, Ali M, Prodromou C, et al. Structure of an Hsp90-Cdc37-Cdk4 complex. Mol Cell. 2006;23:697-707 pubmed
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    ..The MAP kinase was detected by western blot. Cyclin D1 and CDK4 (cyclin dependent kinase 4) proteins was measured by immunocytochemistry...
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    ..Survival analysis of CDK4 amplification revealed a highly significant association with a worse clinical outcome (P = ...