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Expression of cells a mutant CDK4 (CDK4(R24C)) in beta-cells enhanced beta-cell replication. CDK4(R24C) also dampened compensatory beta-cell neogenesis in larvae and improved glucose tolerance in adult zebrafish.
The combination of ribociclib, a dual inhibitor of cyclin-dependent kinase (CDK) 4 and 6, and the ALK inhibitor ceritinib demonstrated higher cytotoxicity and synergy scores (P = 0.006) in cell lines with ALK mutations as compared with cell lines lacking mutations or alterations in ALK .
Results showed that CDK4 expression was up-regulated in colorectal carcinoma and suggested that cdc37 (显示 CDC37 蛋白) increased the stability of CDK4 to activate RB1 (显示 RB1 蛋白) which ultimately promotes G1-S transition.
Data show that sulfatase 1 (hSulf-1 (显示 SULF1 蛋白)) overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT (显示 AKT1 蛋白)) phosphorylation and limiting cyclin dependent kinase 4 (CDK4) nuclear import.
we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2.
CDK4/6 inhibition suppressed cell cycle progression of ER+/HER2 (显示 ERBB2 蛋白)- brreast cancer models.
Proliferating tumor stem cells with high telomerase expression are suitable targets for CDK4/6 inhibitor, palbociclib.
PRMT5 (显示 PRMT5 蛋白) inhibited the interaction between CDK4 and CDKN2A and then activated the CDK4-RB-E2F (显示 E2F1 蛋白) pathway in hepatocellular carcinoma cells under glucose induction.
This is the first clinical study exploring the use of a CDK4/6 inhibitor in a pediatric population. In this phase I study, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of single-agent ribociclib in pediatric patients with neuroblastoma, MRTs, or other cancers with documented cyclin D-CDK4/6-INK4-retinoblastoma pathway aberrations
This study demonstrated that IB-MECA induces G1 phase cell cycle arrest through Cyclin D1 (显示 CCND1 蛋白)/CDK4-mediated pathway in ovarian cancer cells.
Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth.
The in vitro cultivation of cumulus cells was associated with cell proliferation and that Cx43 (显示 GJA1 蛋白) and Cdk4 gene expression was upregulated after in vitro cultivation, resulting in significantly higher protein levels.
Activation of cdk4 triggers NAFLD.
This novel mechanism explains how CDK4 promotes anabolism by blocking catabolic processes (FAO) that are activated by AMPK (显示 PRKAA1 蛋白).
PD 0332991 (PD), an FDA-approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents radiation-induced lethal intestinal injury in mice. Treating mice with PD or a structurally distinct CDK4/6 inhibitor prior to radiation blocked proliferation and crypt apoptosis and improved crypt regeneration.
The results demonstrate a unique CDK4-mediated mitochondrial communication that allows cells to sense environmental genotoxic stress and boost mitochondrial homeostasis by enhancing phosphorylation and activation of MnSOD (显示 SOD2 蛋白).
a crucial role of RXRa in suppression of UVB-induced melanomas in the context of driver mutations such as activated CDK4(R24C/R24C) or oncogenic NRAS(Q61K) and altered expression of p53 and PTEN
Our data indicate that Cdk2 (显示 CDK2 蛋白) and Cdk4 play important overlapping roles in homeostatic and stress hematopoiesis, which need to be considered when using broad-spectrum cyclin-dependent kinase (显示 CDK1 蛋白) inhibitors for cancer therapy.
CDK4 is a critical downstream target of MEN1-dependent tumor suppression and is required for tumorigenic proliferation in the pituitary and pancreatic islet, whereas CDK2 (显示 CDK2 蛋白) is dispensable for tumorigenesis in these neuroendocrine cell types.
Cdk4 and Cdk6 (显示 CDK6 蛋白) cooperate in hematopoietic tumor development and suggest a role for Cdk6 (显示 CDK6 蛋白) in sequestering INK4 proteins away from Cdk4.
CDK4 seems to be expressed as multiple proteins that respond differently to different shRNAs, and have previously unrecognized functions at the S-G 2/M phases of the cell cycle via mechanisms independent of binding to CCND and RB.
CCND1 mRNA expression is increased by FGF9 in bovine theca cells and granulosa cells.
The results indicate that the precise regulation of neuronal Cdk4 activity is important to limit mitochondrial reactive oxygen species production and prevent neurodegeneration.
CDK4 activity regulates mitobiogenesis by the activation of NRF-1 (显示 NRF1 蛋白) and consequent induction of Tfam (显示 TFAM 蛋白) and mitochondrial ribossomal transcription.
Delg and cyclin D/Cdk4 have roles in nutritional control of mitochondrial biogenesis in the Drosophila adipose tissue
Cyclin D-cdk4 is not a master regulator of cell multiplication in Drosophila embryos
mRpL12 (显示 MRPL12 蛋白) is required for CycD/Cdk4-induced cell growth
Our data suggest that the growth-specific function of CycD/Cdk4 is conserved from arthropods to mammals.
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported.
cell division protein kinase 4
, cyclin dependent kinase 4
, serine/threonine kinase
, Cell division protein kinase 4
, Cyclin-dependent kinase 4/6
, cyclin-dependent kinase 4
, protein kinase-like 53C