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  • tumor
  • Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity. (dkfz.de)
  • Mitogen-dependent, cyclin D-dependent kinases (cdk4 and cdk6) phosphorylate the retinoblastoma (Rb) tumor suppressor protein, helping to cancel its growth-inhibitory effects and enabling E2F transcription factors to activate genes required for entry into the DNA synthetic phase (S) of the cell division cycle. (aacrjournals.org)
  • Lesions in the p16 - cyclin D-CDK4 - Rb and ARF - Mdm2 - p53 pathways occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of most, if not all, cancer cells. (aacrjournals.org)
  • Background: Chk1 kinase acts downstream of ATM/ATR kinase and plays an important role in DNA damage checkpoint control, embryonic development, and tumor suppression (1). (cellsignal.com)
  • INK4a
  • Labels above denote the relative rate of accumulation of changes (e.g., exon 2 gains nonsynonymous mutations 3.2 times faster than its interacting gene, CDK4, whereas the rates of amino acid substitutions between the two exons of INK4a are equal). (nih.gov)
  • p16 INK4A , originally identified as a protein associating with CDK4 in transformed cells ( 57 ), was cloned in a two-hybrid screen for proteins interacting with CDK4 ( 48 ). (asm.org)
  • PCNA
  • Furthermore, the SC down-regulated the expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell factor) in the BC cell lines. (jcancer.org)
  • Microarray analysis revealed several differentially expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC-promoted BC cell death and motility. (jcancer.org)
  • anticancer
  • Recent studies demonstrating clear anticancer efficacy and reduced toxicity of CDK4/6 inhibitors such as palbociclib and multi-CDK inhibitors such as dinaciclib have rejuvenated the field. (aspetjournals.org)
  • The facts that myriad cancer types show aberrance in INK4-CDK4/6-cyclin D-Rb-E2F pathway, & the rapidly emerging positive clinical data of pharmacological inhibitors have validated CDK4/6 as anticancer drug targets. (aacrjournals.org)
  • proliferation
  • Genetic rescue of Cdk4 null mice restores pancreatic beta-cell proliferation but not homeostatic cell number. (dkfz.de)
  • mitogenic
  • Moreover, decreased kinase activity was accompanied by a twofold increase in levels of p57 Kip2 protein, but not p21 Cip1 or p27 Kip1 , suggesting that p57 Kip2 mediates PACAP anti-mitogenic effects. (jneurosci.org)
  • complex
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • This latter result was clearly demonstrated by in vitro kinase assays showing that the p25-Cdk5 complex in our cell system phosphorylates Rb directly without the need for any intermediary kinase activity. (biologists.org)
  • However, no mechanisms have been determined by which this kinase complex triggers its neurotoxicity. (biologists.org)