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

Top Publications

  1. Alvira D, Tajes M, Verdaguer E, de Arriba S, Allgaier C, Matute C, et al. Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons. Neuroscience. 2007;146:350-65 pubmed
    ..We show a distinct increase in the expression of the cell cycle proteins cyclin D, cyclin E, cdk2, cdk4 and the transcription factor E2F-1 following a MPP+ treatment of CGNs...
  2. Xiao L, Rao J, Zou T, Liu L, Marasa B, Chen J, et al. Induced JunD in intestinal epithelial cells represses CDK4 transcription through its proximal promoter region following polyamine depletion. Biochem J. 2007;403:573-81 pubmed
    ..b>CDK4 (cyclin-dependent kinase 4) is essential for the G1- to S-phase transition during the cell cycle and its expression ..
  3. Xiao L, Rao J, Zou T, Liu L, Yu T, Zhu X, et al. Induced ATF-2 represses CDK4 transcription through dimerization with JunD inhibiting intestinal epithelial cell growth after polyamine depletion. Am J Physiol Cell Physiol. 2010;298:C1226-34 pubmed publisher
    ..Here, we reported that induced ATF-2 following polyamine depletion repressed CDK4 gene transcription in IECs by increasing formation of the ATF-2/JunD heterodimers...
  4. Cui L, Shi Y, Qian J, Dai G, Wang Y, Xia Y, et al. Deregulation of the p16-cyclin D1/cyclin-dependent kinase 4-retinoblastoma pathway involved in the rat bladder carcinogenesis induced by terephthalic acid-calculi. Urol Res. 2006;34:321-8 pubmed
    ..Immunohistochemical examination revealed overexpression of cyclin D1, cyclin-dependent kinase 4 (Cdk4), retinoblastoma (Rb), and proliferating cell nuclear antigen (PCNA) in bladder preneoplastic and neoplastic ..
  5. Quentin T, Henke C, Korabiowska M, Schlott T, Zimmerman B, Kunze E. Altered mRNA expression of the Rb and p16 tumor suppressor genes and of CDK4 in transitional cell carcinomas of the urinary bladder associated with tumor progression. Anticancer Res. 2004;24:1011-23 pubmed
    ..Rb) and p16 (CDKN2, INK4A, MTS1) genes as well as of the proto-oncogene cyclin D-dependent kinase 4 (CDK4) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and ..
  6. Aikawa T, Segre G, Lee K. Fibroblast growth factor inhibits chondrocytic growth through induction of p21 and subsequent inactivation of cyclin E-Cdk2. J Biol Chem. 2001;276:29347-52 pubmed
    ..Taken together, FGF's growth inhibitory effects of chondrocytes appear to be mediated at least partially through p21 induction and the subsequent inactivation of cyclin E-Cdk2 and activation of pRb. ..
  7. Suh D, Yoon M, Choi K, Kim J. Significance of E2F-1 overexpression in epithelial ovarian cancer. Int J Gynecol Cancer. 2008;18:492-8 pubmed
    ..We investigated overexpression of E2F-1 and alterations of p16(INK4a), cyclin D1, CDK4, and pRb using immunohistochemistry and tissue microarray methods in 72 EOC patients...
  8. Tanguay D, Chiles T. Regulation of the catalytic subunit (p34PSK-J3/cdk4) for the major D-type cyclin in mature B lymphocytes. J Immunol. 1996;156:539-48 pubmed
    We examined the expression of the cyclin-dependent kinase 4, p34PSK-J3/cdk4 protein, in small dense, activated, and proliferating primary B lymphocytes. A small steady state level of cdk4 synthesis was detected in resting B cells...
  9. Beauchamp R, Sheng H, Shao J, Thompson E, Ko T. Intestinal cell cycle regulations. Interactions of cyclin D1, Cdk4, and p21Cip1. Ann Surg. 1996;223:620-7; discussion 627-8 pubmed contact inhibition, and determined whether increases in the relative amount of p21 associated with cyclin D/Cdk4 protein complexes were associated with cell growth arrest...

More Information


  1. Diehl J, Yang W, Rimerman R, Xiao H, Emili A. Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase. Mol Cell Biol. 2003;23:1764-74 pubmed
    ..Hsc70 associates with newly synthesized cyclin D1 and is a component of a mature, catalytically active cyclin D1/CDK4 holoenzyme complex...
  2. Capaldo C, Koch S, Kwon M, Laur O, Parkos C, Nusrat A. Tight function zonula occludens-3 regulates cyclin D1-dependent cell proliferation. Mol Biol Cell. 2011;22:1677-85 pubmed publisher
    ..This study highlights an important new role for ZO family TJ proteins in regulating epithelial cell proliferation through stabilization of cyclin D1 during mitosis. ..
  3. Zhang T, Liu W, Saunee N, Breslin M, Lan M. Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest. J Biol Chem. 2009;284:5574-81 pubmed publisher
    ..pull-down and co-immunoprecipitation revealed that INSM1 binding to cyclin D1 interrupts its association with CDK4 and induces hypophosphorylation of the retinoblastoma protein...
  4. Obaya A, Kotenko I, Cole M, Sedivy J. The proto-oncogene c-myc acts through the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) to facilitate the activation of Cdk4/6 and early G(1) phase progression. J Biol Chem. 2002;277:31263-9 pubmed
    ..cycle requires mitogenic stimulation, which ultimately leads to the activation of cyclin-dependent kinases 4 and 6 (Cdk4/6). Cdk4/6 activity is promoted by D-type cyclins and opposed by Cdk inhibitor proteins...
  5. Faussillon M, Monnier L, Junien C, Jeanpierre C. Frequent overexpression of cyclin D2/cyclin-dependent kinase 4 in Wilms' tumor. Cancer Lett. 2005;221:67-75 pubmed
    The expression status of the three cyclin D genes (CCND1, CCND2 and CCND3), the two cyclin D-dependent kinase genes (CDK4 and CDK6) and the p16(INK4a) gene was studied in a series of 47 Wilms' tumors, 16 normal mature kidneys and two ..
  6. Hurlin P, Zhou Z, Toyo oka K, Ota S, Walker W, Hirotsune S, et al. Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis. EMBO J. 2003;22:4584-96 pubmed
    ..Defective cell cycle control in the absence of Mnt is linked to upregulation of Cdk4 and cyclin E and the Cdk4 gene appears to be a direct target of Mnt-Myc antagonism...
  7. Cheung T, Yu M, Lo K, Yim S, Chung T, Wong Y. Alteration of cyclin D1 and CDK4 gene in carcinoma of uterine cervix. Cancer Lett. 2001;166:199-206 pubmed
    Amplification and overexpression of cyclin D1 and CDK4 genes in cervical carcinoma were studied by semi-quantitative differential polymerase chain reaction assay and an immunostaining technique, respectively...
  8. Terada Y, Kobayashi T, Kuwana H, Tanaka H, Inoshita S, Kuwahara M, et al. Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A. J Am Soc Nephrol. 2005;16:2296-305 pubmed
    ..induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities. The presence of CYP11B2 and 11beta-HSD2 mRNA in rat mesangial cells also was shown...
  9. Hinrichsen R, Hansen A, Haunsø S, Busk P. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy. Cell Prolif. 2008;41:813-29 pubmed publisher
    ..In the present study, by immunohistochemistry with a phosphorylation-specific antibody, we found that cyclin D-cdk4/6-phosphorylated retinoblastoma protein (pRb) during hypertrophy and expression of an unphosphorylatable pRb mutant ..
  10. 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
    ..It has become standard practice to bypass the effects of p16(INK4a) by overexpressing CDK4 or a variant form that is unable to bind to INK4 proteins...
  11. Li C, Xing T, Tang M, Yong W, Yan D, Deng H, et al. Involvement of cyclin D1/CDK4 and pRb mediated by PI3K/AKT pathway activation in Pb2+ -induced neuronal death in cultured hippocampal neurons. Toxicol Appl Pharmacol. 2008;229:351-61 pubmed publisher
    ..The present study sought to examine the obligate nature of cyclin D1/cyclin-dependent kinase 4 (CDK4), phosphorylation of its substrate retinoblastoma protein (pRb) and its select upstream signal phosphoinositide 3-..
  12. 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...
  13. Santiago F, Ishii H, Shafi S, Khurana R, Kanellakis P, Bhindi R, et al. Yin Yang-1 inhibits vascular smooth muscle cell growth and intimal thickening by repressing p21WAF1/Cip1 transcription and p21WAF1/Cip1-Cdk4-cyclin D1 assembly. Circ Res. 2007;101:146-55 pubmed
    ..YY1 inhibits p21(WAF1/Cip1) transcription, prevents assembly of a p21(WAF1/Cip1)-cdk4-cyclin D1 complex, and blocks downstream pRb(Ser249/Thr252) phosphorylation and expression of PCNA and TK-1...
  14. Mao C, Xiong M, Liu Y, Shen S, Du X, Yang X, et al. Synthetic lethal therapy for KRAS mutant non-small-cell lung carcinoma with nanoparticle-mediated CDK4 siRNA delivery. Mol Ther. 2014;22:964-73 pubmed publisher
    ..exploited a new therapeutic strategy based on the synthetic lethal interaction between cyclin-dependent kinase 4 (CDK4) downregulation and the KRAS mutation to deliver micellar nanoparticles (MNPs) containing small interfering RNA ..
  15. Sanphui P, Pramanik S, Chatterjee N, Moorthi P, Banerji B, Biswas S. Efficacy of cyclin dependent kinase 4 inhibitors as potent neuroprotective agents against insults relevant to Alzheimer's disease. PLoS ONE. 2013;8:e78842 pubmed publisher
    ..We and others have shown that Cyclin dependent kinase 4 (Cdk4) is activated in AD brain and is required for neuron death...
  16. Yamamoto S, Kohsaka S, Nakajima K. Role of cell cycle-associated proteins in microglial proliferation in the axotomized rat facial nucleus. Glia. 2012;60:570-81 pubmed publisher
    ..The induced cyclin A was immunohistochemically recognized in microglia. Cdk2 and Cdk4 were also detected in the facial nucleus. The CdkI p21 was elevated 5 days after axotomy...
  17. Cho F, Phillips K, Khan S, Weaver T. Cloning of the rat cyclin-dependent kinase 4 cDNA: implication in proliferation-dependent expression in rat tissues. Biochem Biophys Res Commun. 1993;191:860-5 pubmed
    ..Northern blot analyses of pre- and postnatal rat tissues show that rat cdk4 is expressed in a developmentally regulated pattern in all tissues examined...
  18. Sherr C. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 2000;60:3689-95 pubmed
    ..Mitogen-dependent, cyclin D-dependent kinases (cdk4 and cdk6) phosphorylate the retinoblastoma (Rb) tumor suppressor protein, helping to cancel its growth-inhibitory ..
  19. Gao C, Rampalli A, Cai H, He H, Zelenka P. Changes in cyclin dependent kinase expression and activity accompanying lens fiber cell differentiation. Exp Eye Res. 1999;69:695-703 pubmed
    ..was undertaken to explore the expression and regulation of six additional members of the Cdk family (Cdk2, Cdk3, Cdk4, Cdk6, Cdk7 and Cdk8) during lens differentiation...
  20. Wu Y, Lin Y, Lu T. [Effects of Jiangu granule containing serum on the cyclins in rat's osteoblast at G1 phase]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010;30:966-9 pubmed
    ..Cell generation cycle was detected by flow cytometry, and expressions of Cyclin D1, cyclin-dependent kinase 4 (CDK4), oncogene protein (P21) in the osteoblast were detected dynamically using immuno-cytochemical and RT-PCR technique...
  21. Medema R, Herrera R, Lam F, Weinberg R. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A. 1995;92:6289-93 pubmed
    ..These data not only show that the presence of pRB is crucial for growth suppression by p16ink4 but also indicate that the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle. ..
  22. Tamamori Adachi M, Ito H, Nobori K, Hayashida K, Kawauchi J, Adachi S, et al. Expression of cyclin D1 and CDK4 causes hypertrophic growth of cardiomyocytes in culture: a possible implication for cardiac hypertrophy. Biochem Biophys Res Commun. 2002;296:274-80 pubmed
    ..In this study, we investigated a role of cyclin D1 and CDK4, a positive regulator of cell cycle, in cultured neonatal rat cardiomyocyte hypertrophy...
  23. Yang S, Leow C, Tan T. Expression patterns of cytokine, growth factor and cell cycle-related genes after partial hepatectomy in rats with thioacetamide-induced cirrhosis. World J Gastroenterol. 2006;12:1063-70 pubmed
    ..After hepatectomy, the cirrhotic remnant expressed significantly lower levels of cyclin D1, its kinase partner, cdk4, and cyclin E as compared to the controls up to 72 h post hepatectomy...
  24. Gattringer B. [Retrospective study of one year of family therapy in a neurological practice (author's transl)]. Nervenarzt. 1977;48:326-30 pubmed
  25. Calvisi D, Pinna F, Ladu S, Muroni M, Frau M, Demartis I, et al. The degradation of cell cycle regulators by SKP2/CKS1 ubiquitin ligase is genetically controlled in rodent liver cancer and contributes to determine the susceptibility to the disease. Int J Cancer. 2010;126:1275-81 pubmed publisher
  26. Schmidt B, Rose A, Steinhoff C, Strohmeyer T, Hartmann M, Ackermann R. Up-regulation of cyclin-dependent kinase 4/cyclin D2 expression but down-regulation of cyclin-dependent kinase 2/cyclin E in testicular germ cell tumors. Cancer Res. 2001;61:4214-21 pubmed
    ..Therefore, testicular GCTs were analyzed as to the expression of CDK2, CDK4, CDK6, and the expression of their catalytic partners cyclins D1, D2 and E by semiquantitative reverse ..
  27. Atkins D, Gingert C, Justenhoven C, Schmahl G, Bonato M, Brauch H, et al. Concomitant deregulation of HIF1alpha and cell cycle proteins in VHL-mutated renal cell carcinomas. Virchows Arch. 2005;447:634-42 pubmed
    ..VHL mutations/hypermethylation, over-expression of HIF1alpha was parallelled by up-regulation of cyclin D1 and CDK4 and down-regulation of p21 and p27...
  28. Gillam M, Nimbalkar D, Sun L, Christov K, Ray D, Kaldis P, et al. MEN1 tumorigenesis in the pituitary and pancreatic islet requires Cdk4 but not Cdk2. Oncogene. 2015;34:932-8 pubmed publisher
    ..We and others previously demonstrated that adult mice deficient for the Cyclin D partner CDK4 (Cdk4(-/-) mice) exhibit hypoplasia in the pituitary and pancreatic islet due to primary postnatal defects in ..
  29. Lagarrigue S, Lopez Mejia I, Denechaud P, Escoté X, Castillo Armengol J, Jimenez V, et al. CDK4 is an essential insulin effector in adipocytes. J Clin Invest. 2016;126:335-48 pubmed publisher
    ..Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology...
  30. Martin J, Hunt S, Dubus P, Sotillo R, Néhmé Pélluard F, Magnuson M, et al. Genetic rescue of Cdk4 null mice restores pancreatic beta-cell proliferation but not homeostatic cell number. Oncogene. 2003;22:5261-9 pubmed
    Lack of Cdk4 expression in mice leads to insulin-deficient diabetes and female infertility owing to a reduced number of pancreatic beta cells and prolactin-producing pituitary lactotrophs, respectively...
  31. Bonin S, Brunetti D, Benedetti E, Gorji N, Stanta G. Expression of cyclin-dependent kinases and CDC25a phosphatase is related with recurrences and survival in women with peri- and post-menopausal breast cancer. Virchows Arch. 2006;448:539-44 pubmed
    ..High expression levels of CDK2, CDK4 and CDC25a were related to tumour recurrence...
  32. Wang Z, Xie Y, Zhang L, Zhang H, An X, Wang T, et al. Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition. Cell Struct Funct. 2008;33:171-83 pubmed
    ..timing of the G1-S transition in mammalian cell lines revealed acceleration with overexpression of cyclin D2 and Cdk4. Immunolocalization assays revealed that cyclin D2 and Cdk4 formed a complex in the cytoplasm and approached the ..
  33. Lee S, Kim W, Moon S. TNF-alpha regulates vascular smooth muscle cell responses in genetic hypertension. Int Immunopharmacol. 2009;9:837-43 pubmed publisher
    ..The G1 cell cycle-associated proteins such as cyclin D1, cyclin E, CDK2 and CDK4, and kinase activities associated with CDK2 and CDK4, were increased in SHR-derived VSMC...
  34. Meenakshisundaram R, Gragnoli C. CDK4 IVS4-nt40G-->A and T2D-associated obesity in Italians. J Cell Physiol. 2009;221:273-5 pubmed publisher
    ..Cyclin-dependent kinase 4 (CDK4) mediates with D-type cyclins entry of cells into cell cycle in response to external stimuli...
  35. Bem Z, Birecka A. [A rare type of bone involvement in scleroderma (author's transl)]. Pol Przegl Radiol Med Nukl. 1978;42:115-7 pubmed
  36. Xiao L, Cui Y, Rao J, Zou T, Liu L, Smith A, et al. Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1 and microRNA-222 by polyamines. Mol Biol Cell. 2011;22:3055-69 pubmed publisher
    ..Here we provide evidence that polyamines promote the translation of cyclin-dependent kinase 4 (CDK4) by the action of CUG-binding protein 1 (CUGBP1) and microRNA-222 (miR-222) in intestinal epithelial cells...
  37. Nomura Komoike K, Saitoh F, Komoike Y, Fujieda H. DNA Damage Response in Proliferating Müller Glia in the Mammalian Retina. Invest Ophthalmol Vis Sci. 2016;57:1169-82 pubmed publisher
    ..Our findings suggest that the DNA damage response induced by unscheduled cell cycle reentry may be one of the mechanisms that limit the proliferative and regenerative capacity of Müller glia in the mammalian retina. ..
  38. Gao Y, Xue X, Li J, Wang N. [Expression and roles of CDK4 and p21 in lung tissues of premature rats with hyperoxia-induced chronic lung disease]. Zhongguo Dang Dai Er Ke Za Zhi. 2007;9:595-600 pubmed
    ..The aim of the study was to explore the relationship of the expression of cyclin dependent kinase 4 (CDK4) mRNA and cyclin dependent kinase inhibitor (CDKI) p21 mRNA with lung cell proliferation...
  39. Semczuk A, Miturski R, Skomra D, Jakowicki J. Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features. Arch Gynecol Obstet. 2004;269:104-10 pubmed
    ..Currently, we assessed the expression of cell-cycle regulatory proteins (pRb, cyclin D1, p16(INK4A) and cdk4) in 48 sporadic endometrial cancers, and investigated these tumors for a possible relationship between aberrant ..
  40. Meyerson M, Harlow E. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol. 1994;14:2077-86 pubmed
    ..This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression.
  41. Kikuchi M, Harris D, Obara Y, Senoo T, Joyce N. p27kip1 Antisense-induced proliferative activity of rat corneal endothelial cells. Invest Ophthalmol Vis Sci. 2004;45:1763-70 pubmed
    ..No changes in protein level were observed for CDK2, CDK4, p21(cip1), or p15(INK4B)...
  42. Tang L, Contractor T, Clausen R, Klimstra D, Du Y, Allen P, et al. Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6. Clin Cancer Res. 2012;18:4612-20 pubmed publisher
    ..A majority of tumors expressed high amounts of Cdk4 or its partner protein cyclin D1...
  43. Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci. 2005;30:630-41 pubmed
    ..Recent genetic evidence obtained with gene-targeted mice has shown that Cdk4 and Cdk6 are not needed for entry into the cell cycle after mitogenic stimuli and organogenesis; however, they are ..
  44. Yan J, Brown T. Cell proliferation and expression of cell cycle regulatory proteins that control the G1/S transition are age dependent and lobe specific in the Brown Norway rat model of prostatic hyperplasia. Endocrinology. 2008;149:193-207 pubmed
    ..In conclusion, rates of cell proliferation and levels of cell-cycle regulatory proteins that control the G1/S transition exhibit lobe-specific and age-dependent differences in response to androgens. ..
  45. Wagner M, Greten F, Weber C, Koschnick S, Mattfeldt T, Deppert W, et al. A murine tumor progression model for pancreatic cancer recapitulating the genetic alterations of the human disease. Genes Dev. 2001;15:286-93 pubmed
    ..Activation of Ras and Erk causes induction of cyclin D1-Cdk4 without increase of cyclin E or PCNA in ductal lesions...
  46. Boylan J, Gruppuso P. D-type cyclins and G1 progression during liver development in the rat. Biochem Biophys Res Commun. 2005;330:722-30 pubmed
    ..G1 requires the activity of signaling complexes containing cyclins (D- or E-type) and cyclin-dependent kinases (CDK4/6 and CDK2, respectively)...
  47. Rane S, Dubus P, Mettus R, Galbreath E, Boden G, Reddy E, et al. Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia. Nat Genet. 1999;22:44-52 pubmed
    To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule ..
  48. Miyawaki K, Inoue H, Keshavarz P, Mizuta K, Sato A, Sakamoto Y, et al. Transgenic expression of a mutated cyclin-dependent kinase 4 (CDK4/R24C) in pancreatic beta-cells prevents progression of diabetes in db/db mice. Diabetes Res Clin Pract. 2008;82:33-41 pubmed publisher rectify the hyperglycemic state in obese insulin resistant db/db mice, a transgenic line was generated (db/db-CDK4(R24C)) that expresses a constitutively active form of cyclin-dependent kinase 4 (CDK4/R24C) under the control of ..
  49. Zhang T, Nanney L, Luongo C, Lamps L, Heppner K, DuBois R, et al. Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in intestinal adenomas from multiple intestinal neoplasia (Min) mice and human familial adenomatous polyposis patients. Cancer Res. 1997;57:169-75 pubmed
    ..of multiple intestinal neoplasia (Min) mice and human FAP patients, the expression and distribution of cyclin D1, Cdk4, and cell proliferative activity (5-bromo-2'-deoxyuridine incorporation) in normal and adenomatous intestinal ..
  50. Smith E, Frenkel B, Schlegel R, Giordano A, Lian J, Stein J, et al. Expression of cell cycle regulatory factors in differentiating osteoblasts: postproliferative up-regulation of cyclins B and E. Cancer Res. 1995;55:5019-24 pubmed
    ..Consistent with their role in cell cycle progression, cdc2 and cdk2 decrease postproliferatively. However, cdk4 and cyclins A, B, and D1 persist in confluent cells...
  51. Grundschober C, Delaunay F, Pühlhofer A, Triqueneaux G, Laudet V, Bartfai T, et al. Circadian regulation of diverse gene products revealed by mRNA expression profiling of synchronized fibroblasts. J Biol Chem. 2001;276:46751-8 pubmed
    ..We have classified these circadian genes in seven clusters according to their phase of cycling. Our pathway analysis of the mRNA profiling data strongly suggests a direct link between circadian rhythm and cell cycle. ..
  52. Meenakshisundaram R, Piumelli N, Pierpaoli L, Gragnoli C. CDK4 IVS4-nt40G-->A SNP and type 2 diabetes in Italians. Diabetes Res Clin Pract. 2009;86:e28-30 pubmed publisher
    As cyclin-dependant kinase 4 (CDK4) regulates beta cell proliferation, it may confer T2D risk...
  53. Hu M, Deshpande A, Schlichting N, Hinds E, Mao C, Dose M, et al. CDK6 kinase activity is required for thymocyte development. Blood. 2011;117:6120-31 pubmed publisher
    ..This role of CDK6 as a downstream mediator of Notch identifies CDK6 kinase activity as a potential therapeutic target in human lymphoid malignancies. ..
  54. Cao W, Li Y, Li M, Zhang X, Liao M. Txn1, Ctsd and Cdk4 are key proteins of combination therapy with taurine, epigallocatechin gallate and genistein against liver fibrosis in rats. Biomed Pharmacother. 2017;85:611-619 pubmed publisher
    ..Three differentially expressed proteins (Txn1, Ctsd and Cdk4) involved in antioxidant defense system and the activation and proliferation of hepatic stellate cell were selected ..
  55. Simon R, Struckmann K, Schraml P, Wagner U, Forster T, Moch H, et al. Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer. Oncogene. 2002;21:2476-83 pubmed
    ..Putative target genes located in this region include MDM2, CDK4, and GLI...
  56. Woo M, Hakem R, Furlonger C, Hakem A, Duncan G, Sasaki T, et al. Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol. 2003;4:1016-22 pubmed
    ..Our genetic and biochemical data demonstrate that caspase-3 is essential in the regulation of B cell homeostasis. ..
  57. Zhang M, Xie R, Hou W, Wang B, Shen R, Wang X, et al. PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin-D1-dependent Runx2 and Runx3 phosphorylation, ubiquitylation and proteasomal degradation. J Cell Sci. 2009;122:1382-9 pubmed publisher
    ..degradation in a dose-dependent manner and that both Myc-tagged Runx3 and endogenous Runx3 interact directly with CDK4 in COS and RCJ3.1C5.18 cells...
  58. Bahnassy A, Zekri A, Alam El Din H, Aboubakr A, Kamel K, El Sabah M, et al. The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated cervical carcinoma. J Egypt Natl Canc Inst. 2006;18:292-302 pubmed
    ..HPV16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin D1, cyclin E, CDK4, cyclin inhibitors (p21 (waf), p27, p16 (INK4A)) and Ki-67 using immunohistochemistry and differential PCR ..
  59. Qiu C, Shan L, Yu M, Snyderwine E. Deregulation of the cyclin D1/Cdk4 retinoblastoma pathway in rat mammary gland carcinomas induced by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res. 2003;63:5674-8 pubmed
    ..Only 1 of 47 carcinomas showed Cdk4 amplification...
  60. Motohashi M, Wakui S, Muto T, Suzuki Y, Shirai M, Takahashi H, et al. Cyclin D1/cdk4, estrogen receptors ? and ?, in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis: immunohistochemical study. J Toxicol Sci. 2011;36:373-8 pubmed
    Hyperproliferative cell growth due to cyclin D1/cdk4, marker of cellular proliferation, is considered to be regulated by the expression of estrogen receptors (ERs)...
  61. Powers S, Mandal M, Matsuda S, Miletic A, Cato M, Tanaka A, et al. Subnuclear cyclin D3 compartments and the coordinated regulation of proliferation and immunoglobulin variable gene repression. J Exp Med. 2012;209:2199-213 pubmed publisher
    ..we demonstrate four distinct nuclear D-type cyclin compartments, including one cyclin D3 fraction associated with CDK4 and another phosphoinositide 3-kinase-regulated fraction not required for proliferation...
  62. 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...
  63. Gallagher J, Yamak A, Kirilenko P, Black S, Bochtler M, Lefebvre C, et al. Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4. Mech Dev. 2014;134:31-41 pubmed publisher
    ..of the carboxy terminal end of GATA4 is provided by the results showing physical and functional interaction with CDK4, including the enhancement of cardiogenic activity of GATA4 by CDK4...
  64. Han A, Song Z, Tong C, Hu D, Bi X, Augenlicht L, et al. Sulindac suppresses beta-catenin expression in human cancer cells. Eur J Pharmacol. 2008;583:26-31 pubmed publisher
    ..In conclusion, our data demonstrated that the efficacy of sulindac in the inhibition of cell proliferation (rather than the induction of apoptosis) might be through the suppression of beta-catenin pathway in human cancer cells. ..
  65. Xie T, Niu Y, Ge K, Lu S. Regulation of keratinocyte proliferation in rats with deep, partial-thickness scald: modulation of cyclin D1-cyclin-dependent kinase 4 and histone H1 kinase activity of M-phase promoting factor. J Surg Res. 2008;147:9-14 pubmed
    ..During wound healing, patterns of cell-cycle control expression differed from those previously known. ..
  66. Park Y, Franklin J, Settle S, Levy S, Chung E, Jeyakumar L, et al. Gene expression profile analysis of mouse colon embryonic development. Genesis. 2005;41:1-12 pubmed
  67. Wierød L, Rosseland C, Lindeman B, Oksvold M, Grøsvik H, Skarpen E, et al. CDK2 regulation through PI3K and CDK4 is necessary for cell cycle progression of primary rat hepatocytes. Cell Prolif. 2007;40:475-87 pubmed
    ..In response to mitogenic stimuli, CDK4 and CDK2 form complexes with cyclins D and E, respectively, and translocate to the nucleus in the late G(1) phase...
  68. Xu L, Di Q, Zhang Y. Cell cycle proteins preceded neuronal death after chronic cerebral hypoperfusion in rats. Neurol Res. 2008;30:932-9 pubmed publisher
    ..The apoptotic cells were assessed by TUNEL method. The expression of cell cycle related proteins, i.e. CDK4 and cyclin B1, were detected by immunohistochemical staining and Western blotting...
  69. An H, Beckmann M, Reifenberger G, Bender H, Niederacher D. Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation. Am J Pathol. 1999;154:113-8 pubmed
    Amplification of the cyclin-dependent kinase 4 (CDK4) gene, located at 12q13-q14, has been found as an alternative genetic alteration to CDKN2A inactivation in various human tumors including malignant gliomas and sarcomas...
  70. Hussein N, Lu J, Casse H, Fontanière S, Morera A, Guittot S, et al. Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-beta pathways in Leydig cell lesions developed in male heterozygous multiple endocrine neoplasia type 1 mutant mice. Endocr Relat Cancer. 2008;15:217-27 pubmed publisher
    ..Furthermore, we found that the expression of p18, p27 and cyclin dependant kinase 4 (Cdk4), targets of TGF-beta pathways, is altered in the Leydig cell lesions...
  71. Liu W, Wu Y, Wang L, Gao L, Wang Y, Liu X, et al. Protein signature for non-small cell lung cancer prognosis. Am J Cancer Res. 2014;4:256-69 pubmed
    ..Twelve of 108 proteins (p-CREB(Ser133), p-ERK1/2(Thr202/Tyr204), Cyclin B1, p-PDK1(Ser241), CDK4, CDK2, HSP90, CDC2p34, ?-catenin, EGFR, XIAP and PCNA) were selected to build the predictor to classify normal and ..