CDK4
GeneName
CDK4
Summary
CDK4, also known as cyclin dependent kinase 4, is a 34 kDa serine/threonine kinase that plays a pivotal role in cell cycle regulation, particularly in the G1/S transition. It forms complexes with cyclins D1, D2, and D3, which are essential for its activation and function. CDK4 is predominantly expressed in the nucleus, where it associates with chromatin and transcription regulator complexes to facilitate the regulation of gene expression and cell division. This kinase is involved in various cellular responses, including those to interleukin-4 and lipopolysaccharide, highlighting its role in signal transduction pathways that influence cell proliferation and differentiation.
Importance
CDK4 is relevant to: - Cancer research due to its role in cell cycle progression and its frequent dysregulation in tumours - Developmental biology as it regulates cell proliferation during tissue growth and differentiation - Therapeutic strategies targeting CDK4/6 in oncology, which have shown promise in treating hormone receptor-positive breast cancer - Understanding cellular responses to external stimuli, contributing to insights in immunology and inflammation
Top Products
For researchers investigating CDK4, we highly recommend the top-selling recombinant antibody, Anti-Cdk4 antibody [EPR4513-32-7] (ab108357). This well-cited product has garnered 207 citations, reflecting its strong reputation in the field. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). This versatility makes it an excellent choice for those seeking reliable and consistent detection of CDK4 in their experiments.
Abcam Product Citation Summary
The data indicates that CDK4 is a significant target in various cancer studies, particularly in human and mouse models. The use of Abcam antibodies in Western blotting highlights the role of CDK4 in cell cycle regulation, apoptosis, and cell proliferation across different cancer types, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma, and acute myeloid leukaemia (AML).
Abcam Product Citation Table
Function
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.
Involvement in disease
Melanoma, cutaneous malignant 3
CMM3
A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B.
Sequence Similarities
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Cellular localization
- Cytoplasm
- Nucleus
- Nucleus membrane
- Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.
Alternative names
Cyclin-dependent kinase 4, Cell division protein kinase 4, PSK-J3, CDK4
Database links
swissprot:P11802 omim:123834 omim:123829 entrezGene:595 entrezGene:1019 entrezGene:896 swissprot:P30281 swissprot:P24385 omim:168461
Other research areas
- Immuno-oncology