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  • Overexpression
  • Disruption of "the Rb pathway" results from direct mutational inactivation of Rb function, by overexpression of cyclin D-dependent kinases, or through loss of p16 INK4a , an inhibitor of the cyclin D-dependent kinases. (aacrjournals.org)
  • In contrast, subtype II ULMS recapitulated high-grade ULMS with higher tumor weight and invasion rate, and was characterized by overexpression of genes involved in the pathway of epithelial to mesenchymal transition and tumorigenesis, such as CDK6 , MAPK13 and HOXA1 . (pubmedcentralcanada.ca)
  • phosphoinositide
  • and ( c ) atypical PKCs (ζ and ι/λ), which are not regulated by phosphatidylserine, diacylglycerol, or Ca 2+ but are activated by 3-phosphoinositides, phosphoinositide-dependent kinase 1, and specific protein-protein interactions, including direct interaction with Ras protein ( 2 ). (aacrjournals.org)
  • Src interacts with a network of intracellular signaling pathways, including the integrin/focal adhesion kinase, β-catenin/Wnt, RAS-MAP/ERK kinase, phosphoinositide 3-kinases-AKT, and Janus-activated kinase-signal transducers and activators of transcription pathways ( 7 ). (aacrjournals.org)
  • Furthermore
  • Furthermore, CDK6-deficient mice were resistant to lymphomagenesis induced by active Akt, a downstream target of Notch signaling. (aacrjournals.org)
  • tumorigenesis
  • To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. (aacrjournals.org)
  • These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. (aacrjournals.org)
  • However, the specific role of CDK6 in thymocyte development is unclear and the effect of CDK6 loss on T-cell tumorigenesis has not been ascertained. (aacrjournals.org)
  • We report that CDK6 acts as a downstream target of Notch and Akt and is essential for T-cell development and tumorigenesis. (aacrjournals.org)
  • Lobule progenitor cells are the cellular targets of MMTV-ErbB2 tumorigenesis and require cyclin D1 activity for their maintenance. (tuftsmedicalcenter.org)
  • hematopoietic
  • Since Runx transcription factors play central roles in hematopoietic, neuronal and osteogenic lineages, this novel, noncanonical Cdk6 function may control terminal differentiation in multiple tissues and cell types. (embopress.org)
  • In early stages, the CDK6 kinase induces a complex transcriptional program to block p53 in hematopoietic cells. (aacrjournals.org)
  • Cdk2
  • Consistent with a key role for CDK6 as a D-cyclin partner in thymocytes, knockout (KO) of CDK4 or CDK2 was shown to have no significant effect on T-cell development ( 11 , 12 ), but significantly decreased thymic cellularity was observed in a CDK6 KO animal ( 13 ). (aacrjournals.org)
  • p27 Kip1 has classically been regarded as a cell cycle inhibitor based on its potent inhibitory activity of cyclin E/Cdk2 ( 42 ) and the observation that its forced expression results in G 1 arrest (reviewed in reference 49 ). (asm.org)
  • Further, a significant amount of p27(Kip1) was co-precipitated with CDK2, CDK4 and CDK6, as detected in immunoprecipitation experiments. (nih.gov)
  • proliferation
  • In contrast, ErbB2- or cyclin D1-overexpressing p27 −/− cells displayed reduced proliferation, anchorage-independent growth, Cdk4 activity, cyclin D1 expression, and cyclin D1 nuclear localization compared to wild-type cells. (asm.org)
  • A cyclin D1 mutation in its nuclear export sequence (T286A) partially rescued nuclear localization of cyclin D1 in p27 −/− cells but did not increase proliferation or Cdk4 kinase activity. (asm.org)
  • However, MMTV - neu/p27 −/− glands showed decreased proliferation, cyclin D1 expression, and Cdk4 activity, as well as markedly prolonged tumor latency, compared to MMTV - neu/p27 +/+ glands. (asm.org)
  • Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6 . (rcsb.org)
  • LNCaP
  • and ( e ) microarray analysis of LNCaP cells carrying kinase-dead MAK mutant showed a significant impediment of AR signaling, indicating that endogenous MAK plays a general role in AR function in prostate cancer cells and likely to be a general coactivator of AR in prostate tissues. (aacrjournals.org)
  • survival
  • It has been shown that Notch-promoted survival and trophic effects in pre-T cells are mediated by the phosphatidylinositol 3-kinase (PI3K)-Akt pathway ( 6 ). (aacrjournals.org)
  • In this study, we tested the role of a specific Src kinase inhibitor on the adhesion, migration, and survival of Waldenstrom macroglobulinemia cells. (aacrjournals.org)