Gene Symbol: cdk6
Description: cyclin dependent kinase 6
Alias: MCPH12, PLSTIRE, cyclin-dependent kinase 6, cell division protein kinase 6, serine/threonine-protein kinase PLSTIRE
Species: human
Products:     cdk6

Top Publications

  1. Russo A, Tong L, Lee J, Jeffrey P, Pavletich N. Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. Nature. 1998;395:237-43 pubmed
    ..The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of ..
  2. 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
    ..In total, our results support clinical trial evaluation of PD-0332991 against newly diagnosed as well as recurrent GBM, and indicate that Rb status is the primary determinant of potential benefit from this therapy. ..
  3. Zhao J, Lin J, Lwin T, Yang H, Guo J, Kong W, et al. microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood. 2010;115:2630-9 pubmed publisher
    ..Furthermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3'-untranslated region...
  4. Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M, et al. miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev. 2009;23:2388-93 pubmed publisher
    ..Here we report that E2F1 directly transactivates miR-449a/b. miR-449a/b targets and inhibits oncogenic CDK6 and CDC25A, resulting in pRb dephosphorylation and cell cycle arrest at G1 phase, revealing a negative feedback ..
  5. Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R, et al. Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 2008;582:1564-8 pubmed publisher
    ..expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6)...
  6. Lettre G, Jackson A, Gieger C, Schumacher F, Berndt S, Sanna S, et al. Identification of ten loci associated with height highlights new biological pathways in human growth. Nat Genet. 2008;40:584-91 pubmed publisher
    ..These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. ..
  7. Ogasawara T, Kawaguchi H, Jinno S, Hoshi K, Itaka K, Takato T, et al. Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6. Mol Cell Biol. 2004;24:6560-8 pubmed
    ..Of the G(1) cell cycle factors examined, the expression of cyclin-dependent kinase 6 (Cdk6) was found to be strongly down-regulated by BMP-2/Smads signaling, mainly via transcriptional repression...
  8. Meyerson M, Harlow E. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol. 1994;14:2077-86 pubmed
    ..Here, we show that the human PLSTIRE gene product is a novel cyclin-dependent kinase, cdk6...
  9. Placke T, Faber K, Nonami A, Putwain S, Salih H, Heidel F, et al. Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood. 2014;124:13-23 pubmed publisher
    ..genetic approach to uncover that AML cells driven by MLL-AF9 are exceptionally reliant on the cell-cycle regulator CDK6, but not its functional homolog CDK4, and that the preferential growth inhibition induced by CDK6 depletion is ..

More Information


  1. Wiedemeyer W, Dunn I, Quayle S, Zhang J, Chheda M, Dunn G, et al. Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM. Proc Natl Acad Sci U S A. 2010;107:11501-6 pubmed publisher
    ..Here, we combined functional genetic screens and comprehensive genomic analyses to identify CDK6 as a GBM oncogene that is required for proliferation and viability in a subset of GBM cell lines and tumors...
  2. Chen D, Law M, Theis J, Gamez J, Caron L, Vrana J, et al. Clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders. Am J Surg Pathol. 2009;33:720-9 pubmed publisher
    Cyclin-dependent protein kinase 6 (CDK6), in cooperation with cyclin Ds, drives cell cycle progression from G1 to S phase through phosphorylation and subsequent inactivation of retinoblastoma 1 protein...
  3. Fiaschi Taesch N, Bigatel T, Sicari B, Takane K, Salim F, Velazquez Garcia S, et al. Survey of the human pancreatic beta-cell G1/S proteome reveals a potential therapeutic role for cdk-6 and cyclin D1 in enhancing human beta-cell replication and function in vivo. Diabetes. 2009;58:882-93 pubmed publisher
    ..Using this model, human beta-cell replication can be induced and studied in vivo. ..
  4. Ayala Y, Misteli T, Baralle F. TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Proc Natl Acad Sci U S A. 2008;105:3785-9 pubmed publisher
    ..Removal of TDP-43 in human cells significantly increases cyclin-dependent kinase 6 (Cdk6) protein and transcript levels...
  5. Mendrzyk F, Radlwimmer B, Joos S, Kokocinski F, Benner A, Stange D, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. J Clin Oncol. 2005;23:8853-62 pubmed
    ..of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively...
  6. Lim J, Mansukhani M, Weinstein I. Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer cells. Proc Natl Acad Sci U S A. 2005;102:5156-61 pubmed
    Cyclin-dependent kinase 6 (CDK6) binds to and is activated by cyclin D1 and thereby enhances the transition of cells through the G1 phase of the cell cycle...
  7. Fahraeus R, Lane D. The p16(INK4a) tumour suppressor protein inhibits alphavbeta3 integrin-mediated cell spreading on vitronectin by blocking PKC-dependent localization of alphavbeta3 to focal contacts. EMBO J. 1999;18:2106-18 pubmed
    ..The cdk6 protein is found to suppress p16(INK4a)-mediated inhibition of spreading and is also shown to localize to the ..
  8. Brotherton D, Dhanaraj V, Wick S, Brizuela L, Domaille P, Volyanik E, et al. Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d. Nature. 1998;395:244-50 pubmed
    The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the p19 INK4d protein has been determined at 1.9 A resolution...
  9. Grossel M, Baker G, Hinds P. cdk6 can shorten G(1) phase dependent upon the N-terminal INK4 interaction domain. J Biol Chem. 1999;274:29960-7 pubmed
    Deregulated activity of cdk4 or cdk6 can lead to inappropriate cellular proliferation and tumorigenesis accompanied by unchecked inactivation of the retinoblastoma tumor suppressor protein...
  10. Meyerson M, Enders G, Wu C, Su L, Gorka C, Nelson C, et al. A family of human cdc2-related protein kinases. EMBO J. 1992;11:2909-17 pubmed
    ..The identification of a large family of cdc2-related kinases opens the possibility of combinatorial regulation of the cell cycle together with the emerging large family of cyclins. ..
  11. Raychaudhuri S, Remmers E, Lee A, Hackett R, Guiducci C, Burtt N, et al. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet. 2008;40:1216-23 pubmed publisher
    ..0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4...
  12. Grossel M, Hinds P. Beyond the cell cycle: a new role for Cdk6 in differentiation. J Cell Biochem. 2006;97:485-93 pubmed
    Over 10 years ago, cdk6 was identified as a new member in a family of vertebrate cdc-2 related kinases...
  13. Konecny G, Winterhoff B, Kolarova T, Qi J, Manivong K, Dering J, et al. Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res. 2011;17:1591-602 pubmed publisher
    ..49, 95% CI 1.00-2.24, P = 0.052). PD-0332991 shows promising biologic activity in ovarian cancer cell lines. Assessment of Rb and p16 expression may help select patients most likely to benefit from CDK4/6 inhibition in ovarian cancer. ..
  14. Ruas M, Gregory F, Jones R, Poolman R, Starborg M, Rowe J, et al. CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms. Mol Cell Biol. 2007;27:4273-82 pubmed
    ..Although CDK4 and CDK6 and their INK4-insensitive variants can extend the life span of HDFs, they also cause a substantial increase in the ..
  15. 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
    ..yet many mesenchymal cells express three seemingly redundant D cyclins and similarly, seemingly redundant Cdk4 and Cdk6 as their kinase partners...
  16. Lee K, Lotterman C, Karikari C, Omura N, Feldmann G, Habbe N, et al. Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer. Pancreatology. 2009;9:293-301 pubmed publisher
  17. Fujimoto T, Anderson K, Jacobsen S, Nishikawa S, Nerlov C. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. EMBO J. 2007;26:2361-70 pubmed
    ..We here show that cyclin-dependent kinase 6 (Cdk6) is specifically expressed in proliferating hematopoietic progenitor cells, and that Cdk6 inhibits transcriptional ..
  18. Pierson J, Hostager B, Fan R, Vibhakar R. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol. 2008;90:1-7 pubmed publisher
    ..Recently increased expression of cyclin dependent kinase 6 (CDK6) was identified as an adverse prognostic marker in medulloblastoma...
  19. van Dekken H, van Marion R, Vissers K, Hop W, Dinjens W, Tilanus H, et al. Molecular dissection of the chromosome band 7q21 amplicon in gastroesophageal junction adenocarcinomas identifies cyclin-dependent kinase 6 at both genomic and protein expression levels. Genes Chromosomes Cancer. 2008;47:649-56 pubmed publisher
    ..1 Mb in 7q21.2, precisely comprising cyclin-dependent kinase 6 (CDK6), a gene involved in cell cycle regulation. A smaller peak was seen at 116.2 Mb in 7q31...
  20. Brito Babapulle V, Gruszka Westwood A, Platt G, Andersen C, Elnenaei M, Matutes E, et al. Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia. Haematologica. 2002;87:357-62 pubmed
    ..breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG k genes in the t(2;7) leading to over-expression of CDK6 protein...
  21. De Snoo F, Hottenga J, Gillanders E, Sandkuijl L, Jones M, Bergman W, et al. Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families. Eur J Hum Genet. 2008;16:1135-41 pubmed publisher
    ..The strongest evidence for an atypical nevus susceptibility gene was mapped to chromosome band 7q21.3 (two-point LOD score=2.751), a region containing candidate gene CDK6.
  22. Lucas J, Domenico J, Gelfand E. Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells. Mol Cancer Res. 2004;2:105-14 pubmed
    ..Here, it is shown that normal human mammary epithelial cells have a high amount of cdk6 protein and activity, but all breast tumor-derived cell lines analyzed had reduced levels, with several having ..
  23. Nagel S, Leich E, Quentmeier H, Meyer C, Kaufmann M, Drexler H, et al. Amplification at 7q22 targets cyclin-dependent kinase 6 in T-cell lymphoma. Leukemia. 2008;22:387-92 pubmed
    ..Expression analysis of genes located within this region identified cyclin-dependent kinase 6 (CDK6) as a potential amplification target...
  24. Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott R, et al. A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer Cell. 2013;24:167-81 pubmed publisher
    In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies...
  25. Schulze Gahmen U, Kim S. Structural basis for CDK6 activation by a virus-encoded cyclin. Nat Struct Biol. 2002;9:177-81 pubmed
    Cyclin from herpesvirus saimiri (Vcyclin) preferentially forms complexes with cyclin-dependent kinase 6 (CDK6) from primate host cells...
  26. Soranzo N, Rivadeneira F, Chinappen Horsley U, Malkina I, Richards J, Hammond N, et al. Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size. PLoS Genet. 2009;5:e1000445 pubmed publisher
    ..Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height. ..
  27. Agirre X, Vilas Zornoza A, Jimenez Velasco A, Martin Subero J, Cordeu L, Garate L, et al. Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia. Cancer Res. 2009;69:4443-53 pubmed publisher
    ..Epigenetic down-regulation of miR-124a induced an up-regulation of its target, CDK6, and phosphorylation of retinoblastoma (Rb) and contributed to the abnormal proliferation of ALL cells both in ..
  28. Ericson K, Krull D, Slomiany P, Grossel M. Expression of cyclin-dependent kinase 6, but not cyclin-dependent kinase 4, alters morphology of cultured mouse astrocytes. Mol Cancer Res. 2003;1:654-64 pubmed
    ..The D-cyclin-associated kinases, cyclin-dependent kinase (cdk) 4 and cdk6, are important regulators of the G(1)-S phase transition and are elevated in several types of cancers, including ..
  29. Huang J, Wu Y, He Y. [Expression of MicroRNA-26a and Its Target Gene CDK6 in Extra-nodal NK/T-Cell Lymphoma]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015;23:1021-5 pubmed publisher
    To explore the expression level of microRNA-26a and its target gene CDK6 in extranodal NK/T-cell lymphoma (ENKTCL) and their possible role in genesis and development of ENKTCL...
  30. Zhang Z, Zhang G, Kong C, Zhan B, Dong X, Man X. METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion. Sci Rep. 2016;6:19261 pubmed publisher
    ..regulates cell proliferation in bladder cancer and reinstates G1/S checkpoint via the coordinated downregulation of CDK6, CDK4 and CCND1, decreased phosphorylation of Rb and subsequent delayed cell cycle progression...
  31. Wang P, Wu T, Zhou H, Jin Q, He G, Yu H, et al. Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway. J Exp Clin Cancer Res. 2016;35:22 pubmed publisher
    ..Furthermore, NEAT1 regulated CDK6 expression in LSCC cells which was mediated by miR-107...
  32. Singh N, Janjanam J, Rao G. p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation. J Biol Chem. 2017;292:14080-14091 pubmed publisher
    ..Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling...
  33. Ciołczyk Wierzbicka D, Gil D, Laidler P. Treatment of melanoma with selected inhibitors of signaling kinases effectively reduces proliferation and induces expression of cell cycle inhibitors. Med Oncol. 2017;35:7 pubmed publisher
    ..effect on the expression of cell cycle regulatory proteins: cyclin D1 and D3, cyclin-dependent kinase CDK4 and CDK6, and cell cycle inhibitors: p16, p21, and p27, was studied at the protein level (western blot)...
  34. Xu G, Li J. CDK4, CDK6, cyclin D1, p16(INK4a) and EGFR expression in glioblastoma with a primitive neuronal component. J Neurooncol. 2018;136:445-452 pubmed publisher
    ..stains with antibodies against proteins that interact with CDK4 in cell cycle regulation, such as CDK6, cyclin D1 and p16(INK4a), were performed on these GBM-PN and GBM cases...
  35. Roncati L, Barbolini G, Sartori G, Siopis E, Pusiol T, Maiorana A. Loss of CDKN2A Promoter Methylation Coincides With the Epigenetic Transdifferentiation of Uterine Myosarcomatous Cells. Int J Gynecol Pathol. 2016;35:309-15 pubmed publisher
    ..This event may result in an inhibition of cdk4/cdk6 activity, stabilizes the tumor suppressor protein p53, and coincides with the transdifferentiation from smooth ..
  36. Park J, Han C, Zhao L, Willingham M, Cheng S. Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model. Endocr Relat Cancer. 2016;23:53-63 pubmed publisher
    ..Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated ..
  37. Maymó Masip E, Fernández Veledo S, Garcia Espana A, Vázquez Carballo A, Tinahones F, Garcia Fuentes E, et al. The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNF?. J Clin Endocrinol Metab. 2013;98:E1323-33 pubmed publisher
    ..In human adipocytes, sTWEAK down-regulates TNF? cytokine production by hampering TNF? intracellular signaling events. The decrease of sTWEAK in severely obese patients may favor the proinflammatory activity elicited by TNF?. ..
  38. Lamb R, Lehn S, Rogerson L, Clarke R, Landberg G. Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity. Cell Cycle. 2013;12:2384-94 pubmed publisher
    ..The significance of these results adds to our general understanding of cancer biology but, most importantly, could be used diagnostically to predict treatment response to cell cycle inhibition in breast cancer. ..
  39. Dozier C, Mazzolini L, CÃ©nac C, Froment C, Burlet Schiltz O, Besson A, et al. CyclinD-CDK4/6 complexes phosphorylate CDC25A and regulate its stability. Oncogene. 2017;36:3781-3788 pubmed publisher
    ..We demonstrate that CyclinD-CDK4/CDK6 complexes mediate the phosphorylation of CDC25A on Ser40 during G1 and that these complexes directly phosphorylate ..
  40. Sang H, Jin Y, Zhang W, Chen L. Downregulation of microRNA-637 Increases Risk of Hypoxia-Induced Pulmonary Hypertension by Modulating Expression of Cyclin Dependent Kinase 6 (CDK6) in Pulmonary Smooth Muscle Cells. Med Sci Monit. 2016;22:4066-4072 pubmed
    ..of this study was to investigate the molecular mechanism by which miR-637 interferes with the expression of CDK6, which contributes to the development of pulmonary hypertension (PH) with chronic obstructive pulmonary disease (..
  41. Shi Y, Qian Z, Zhang S, Li W, Masugi Y, Li T, et al. Cell Cycle Protein Expression in Neuroendocrine Tumors: Association of CDK4/CDK6, CCND1, and Phosphorylated Retinoblastoma Protein With Proliferative Index. Pancreas. 2017;46:1347-1353 pubmed publisher
    ..We evaluated expression of key proteins involved in cell cycle regulation in a large cohort of NETs...
  42. Liu T, Fang Z, Wang G, Shi M, Wang X, Jiang K, et al. Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. Oncol Lett. 2016;11:182-188 pubmed
    ..proteins, including phosphorylated protein kinase B, cyclin D1, cyclin dependent kinase (CDK) 2 and CDK6 were downregulated by BCTC, while phosphorylated glycogen synthase kinase 3Î² was upregulated...
  43. Heger Z, Michalek P, Guran R, Cernei N, Duskova K, Vesely S, et al. Differences in urinary proteins related to surgical margin status after radical prostatectomy. Oncol Rep. 2015;34:3247-55 pubmed
  44. Ortmann B, Bensaddek D, Carvalhal S, Moser S, Mudie S, Griffis E, et al. CDK-dependent phosphorylation of PHD1 on serine 130 alters its substrate preference in cells. J Cell Sci. 2016;129:191-205 pubmed publisher
    ..Here, we demonstrate that PHD1 is phosphorylated by CDK2, CDK4 and CDK6 at S130. This phosphorylation fluctuates with the cell cycle and can be induced through oncogenic activation...
  45. Li S, Xu D, Guo J, Sun Y. Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells. Environ Toxicol. 2016;31:1785-1795 pubmed publisher
    ..showed that endosulfan at 60 Î¼M induced G1 cell cycle arrest, a response attributed to down-regulation of CDK6 and pRb dephosphorylation...
  46. Gong X, Litchfield L, Webster Y, Chio L, Wong S, Stewart T, et al. Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib. Cancer Cell. 2017;32:761-776.e6 pubmed publisher
    ..functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not ..
  47. Ho S, Rao R, To S, Schoch E, Tarapore P. Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer. Endocr Relat Cancer. 2017;24:83-96 pubmed publisher
    ..BPA-exposed cells exhibited increased expression of cyclin-dependent kinase CDK6 and decreased expression of CDK inhibitors (p21Waf1/CIP1 and p27KIP1)...
  48. Liu Y, Fan C, Pu L, Wei C, Jin H, Teng Y, et al. Phloretin induces cell cycle arrest and apoptosis of human glioblastoma cells through the generation of reactive oxygen species. J Neurooncol. 2016;128:217-23 pubmed publisher
    ..cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclinD and cyclinE...
  49. Beck T, Georgopoulos R, Shagisultanova E, Sarcu D, Handorf E, Dubyk C, et al. EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer. Mol Cancer Ther. 2016;15:2486-2497 pubmed
    ..In addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected by CCND1/CDK6-inactivating phosphorylation of RB1 at T356, inversely correlated with expression of EGFR in patient HNSCC samples...
  50. Xu J, Zhang R, Zhao J. The Novel Long Noncoding RNA TUSC7 Inhibits Proliferation by Sponging MiR-211 in Colorectal Cancer. Cell Physiol Biochem. 2017;41:635-644 pubmed publisher
    ..TUSC7 overexpression increased the expression level of CDK6, which is a downstream target of miR-211-3p, in both RNA and protein level...
  51. Fiaschi Taesch N, Salim F, Kleinberger J, Troxell R, Cozar Castellano I, Selk K, et al. Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6. Diabetes. 2010;59:1926-36 pubmed publisher
    ..of the five, alone or in combination, led to variable increases in human beta-cell replication, with the cdk6/cyclin D3 combination being the most robust (15% versus 0.3% in control beta-cells)...
  52. Tay S, Yeo C, Chai C, Chua P, Tan H, Ang A, et al. Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells. J Biol Chem. 2010;285:29231-8 pubmed publisher
    ..On the other hand, the level of cyclin-dependent kinase 6 (CDK6) is dramatically and selectively elevated in parkin-expressing breast cancer cells, the extent of which correlates ..
  53. Kaldis P, Ojala P, Tong L, Mäkelä T, Solomon M. CAK-independent activation of CDK6 by a viral cyclin. Mol Biol Cell. 2001;12:3987-99 pubmed
    ..This KSHV-cyclin activates CDK6, alters its substrate specificity, and renders CDK6 insensitive to inhibition by the cdk inhibitor p16(INK4a)...
  54. Mahajan A, Guo Y, Yuan C, Weghorst C, Tsai M, Li J. Dissection of protein-protein interaction and CDK4 inhibition in the oncogenic versus tumor suppressing functions of gankyrin and P16. J Mol Biol. 2007;373:990-1005 pubmed
  55. Buranrat B, Suwannaloet W, Naowaboot J. Simvastatin potentiates doxorubicin activity against MCF-7 breast cancer cells. Oncol Lett. 2017;14:6243-6250 pubmed publisher
    ..C3 botulinum toxin substrate 1 and numerous downstream proteins including cyclin-dependent kinase (Cdk) 2, Cdk4 and Cdk6. Additionally, simvastatin in combination with doxorubicin significantly induced expression of the cyclin-dependent ..
  56. Jia L, Gu W, Zhang Y, Ji Y, Liang J, Wen Y, et al. The Crosstalk between HDPSCs and HUCMSCs on Proliferation and Osteogenic Genes Expression in Coculture System. Int J Med Sci. 2017;14:1118-1129 pubmed publisher
    ..The proportion of EdU-positive cells increased and the expression of CDK6 and CYCLIN A were up-regulated in cocultured hDPSCs...
  57. Jones R, Ruas M, Gregory F, Moulin S, Delia D, Manoukian S, et al. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. 2007;67:9134-41 pubmed vivo analyses, the R24P variant is specifically defective for binding to CDK4 but remains able to associate with CDK6. Nevertheless, Milan HDFs behave as if they are p16INK4a deficient, in terms of sensitivity to spontaneous and ..
  58. Wu H, Tao J, Li X, Zhang T, Zhao L, Wang Y, et al. MicroRNA-206 prevents the pathogenesis of hepatocellular carcinoma by modulating expression of met proto-oncogene and cyclin-dependent kinase 6 in mice. Hepatology. 2017;66:1952-1967 pubmed publisher
    ..and cellular approaches, we identified cMET (Met proto-oncogene), cyclin D1 (CCND1), and cyclin-dependent kinase 6 (CDK6) as functional targets of microRNA-206...
  59. Iwanaga R, Ozono E, Fujisawa J, Ikeda M, Okamura N, Huang Y, et al. Activation of the cyclin D2 and cdk6 genes through NF-kappaB is critical for cell-cycle progression induced by HTLV-I Tax. Oncogene. 2008;27:5635-42 pubmed publisher
    ..promote cell-cycle progression in resting T cells along with induction of cyclin D2 and cyclin-dependent kinase (cdk6) gene expression...
  60. Selma Dagtas A, Gilbert K. p21(Cip1) up-regulated during histone deacetylase inhibitor-induced CD4(+) T-cell anergy selectively associates with mitogen-activated protein kinases. Immunology. 2010;129:589-99 pubmed publisher
    ..The n-butyrate-induced p21(Cip1)-mediated inhibition of JNK and c-jun represents a novel potential mechanism by which proliferative unresponsiveness was maintained in CD4(+) T cells. ..
  61. Alekseenko A, Wojas Pelc A, Lis G, Furgał Borzych A, Surowka G, Litwin J. Cyclin D1 and D3 expression in melanocytic skin lesions. Arch Dermatol Res. 2010;302:545-50 pubmed publisher
    ..In histopathologically ambiguous cases, lower cyclin D3 expression in dysplastic nevi can be a diagnostic marker for that lesion type. ..
  62. Reiner A, Lettre G, Nalls M, Ganesh S, Mathias R, Austin M, et al. Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT). PLoS Genet. 2011;7:e1002108 pubmed publisher European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21...
  63. Li B, He H, Tao B, Zhao Z, Hu G, Luo C, et al. Knockdown of CDK6 enhances glioma sensitivity to chemotherapy. Oncol Rep. 2012;28:909-14 pubmed publisher
    ..Here, we demonstrate that CDK6, a cell cycle regulator, is significantly upregulated in glioma cells, and the increasing expression of ..
  64. Dai X, Wu Y, Jia X, Chang Y, Wu H, Wang C, et al. hIgD promotes human Burkitt lymphoma Daudi cell proliferation by accelerated G1/S transition via IgD receptor activity. Immunol Res. 2016;64:978-87 pubmed publisher
    ..of the cell cycle at the G1/S transition, and this was accompanied by upregulation of c-myc, cyclin D3, and CDK6 as well as downregulation of p16 mRNA and protein levels...
  65. Bellail A, Olson J, Hao C. SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression. Nat Commun. 2014;5:4234 pubmed publisher
    ..Here we show that CDK6 is modified by small ubiquitin-like modifier-1 (SUMO1) in glioblastoma, and that CDK6 SUMOylation stabilizes the ..
  66. Finn R, Crown J, Lang I, Boer K, Bondarenko I, Kulyk S, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16:25-35 pubmed publisher
    ..A phase 3 trial is currently underway. Pfizer. ..
  67. Wang L, Shao J, Zhang X, Xu M, Zhao J. microRNA-377 suppresses the proliferation of human osteosarcoma MG-63 cells by targeting CDK6. Tumour Biol. 2015;36:3911-7 pubmed publisher
    ..Because cyclin-dependent kinase 6 (CDK6) may be a potential target of miR-377 in osteosarcoma cells, we overexpressed CDK6 and observed that overexpression ..
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    ..Further analysis suggested the key regulator of G1/S transition, cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited CDK6 expression and bound to the 3'UTR of CDK6...
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    ..of synthetic miR-29a mimics into Jurkat cells revealed the downregulation of several predicted targets (CDK6, PXDN, MCL1, PIK3R1, and CXXC6), including targets with roles in active and passive DNA demethylation (such as ..
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    ..Mutations in the TARDPB gene, progranulin gene (PGRNVCP) as well as a gene on chromosome 9p were found. The present paper is a summary on possible involvement of TDP-43 in various neurodegenerative disorders. ..
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    ..The quantitative real-time PCR was applied to validate the expression of miRNA-195. The expression of CDK6 was investigated by the quantitative real-time PCR and immunohistochemistry...
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    ..Furthermore, CDK6 was identified as a novel functional target of miR?200a...
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    Cyclin-dependent kinase 6 (Cdk6) is a D-Cyclin-activated kinase that is directly involved in driving the cell cycle through inactivation of pRB in G? phase...
  74. Kikkawa N, Kinoshita T, Nohata N, Hanazawa T, Yamamoto N, Fukumoto I, et al. microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. Int J Oncol. 2014;44:2085-92 pubmed publisher
    ..Our data showed that cell cycle-related genes (RB1, CDK6, CDC23 and CCND1) were candidate target genes of miR-504...
  75. Raleigh D, Choksi P, Krup A, Mayer W, Santos N, Reiter J. Hedgehog signaling drives medulloblastoma growth via CDK6. J Clin Invest. 2018;128:120-124 pubmed publisher
    ..Hh signaling induced GLI2 binding to the Cdk6 promoter and activated Cdk6 expression, thereby promoting uncontrolled cell proliferation...
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    ..down-regulation of cyclin D3 protein, retinoblastoma hypophosphorylation, loss of cyclin-dependent kinase (cdk) 4, cdk6, and cdk2 activity...