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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.
while mTOR inhibitors restore endocrine sensitivity, CDK4/6 inhibitors may favor the emergence of estrogen receptor 1 (ESR1) mutations resulting in ligand-independent activity of the receptor
Inhibition of CDK4/6 is potentially a highly effective strategy for the treatment of SHH (显示 SHH 蛋白) and MYC (显示 MYC 蛋白)-amplified group 3 medulloblastoma.
SOX12 (显示 SOX12 蛋白) can increase the expression of CDK4 and IGF2BP1 (显示 IGF2BP1 蛋白), which confer malignant phenotypes to Hepatocellular Carcinoma.
Study showed that CDK4 and BCAS2 (显示 BCAS2 蛋白) may be target genes of miR (显示 MLXIP 蛋白)-486 and levels of CDK4 and BCAS2 (显示 BCAS2 蛋白) were both significantly higher in the esophageal cancer tissues and cell lines than levels in the normal tissues and cells.
Results suggest that dysregulation and activation of the cell cycle proteins CDK4/CDK6 (显示 CDK6 蛋白)-CCND1 (显示 CCND1 蛋白)-phospho-RB1 (显示 RB1 蛋白) axis is associated with higher proliferative index in neuroendocrine tumors (NETs).
blocking CDK4 activity efficiently eliminated both normal and chemotherapy-resistant cancer cells in triple negative breast cancers, highlighting CDK4 as a promising novel therapeutic target for these aggressive breast tumors.
Amplification of gene CDK4 is associated with lung adenocarcinoma.
PD-L1 (显示 CD274 蛋白) protein abundance is regulated by cyclin D-CDK4 and the cullin 3 (显示 CUL3 蛋白)-SPOP (显示 SPOP 蛋白) E3 ligase via proteasome-mediated degradation
Ongoing trials of doublet and triplet targeted therapies containing ribociclib seek to identify optimal CDK4/6-based targeted combination regimens for various tumor types and advance the field of precision therapeutics in oncology
Transfection of cells with ClC-3 (显示 CLCN3 蛋白) siRNA decreased the expression of cyclin D1 (显示 CCND1 蛋白), cyclin dependent kinase 4 and 6, and increased the expression of cyclin dependent kinase (显示 CDK1 蛋白) inhibitors (CDKIs), p21 (显示 CDKN1A 蛋白) and p27 (显示 PAK2 蛋白). Pretreatments of cells with p21 (显示 CDKN1A 蛋白) and p27 (显示 PAK2 蛋白) siRNAs depleted the inhibitory effects of ClC-3 (显示 CLCN3 蛋白) siRNA on the expression of CDK4 and CDK6 (显示 CDK6 蛋白), but not on that of cyclin D1 (显示 CCND1 蛋白)
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.
These results indicate that p18 (显示 CDKN2C 蛋白) blocks reprogramming by targeting Cdk4/6-mediated cell cycle regulation.
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.
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