CDK4
CDK4 (cyclin dependent kinase 4, also known as PSK-J3) is a serine/threonine kinase that acts as the catalytic subunit of cyclin D-CDK4 complexes. It phosphorylates retinoblastoma family proteins and drives progression through the G1 phase of the cell cycle. Browse Assay Genie's current range of CDK4 research reagents below, or read on for the biology behind the target.
CDK4 is the Ser/Thr kinase component of cyclin D-CDK4 complexes. These complexes phosphorylate and inhibit members of the retinoblastoma (RB) protein family, including RB1, and so regulate the G1/S transition. CDK4 hypophosphorylates RB1 in early G1. This allows the transcription factor E2F to dissociate from RB/E2F complexes, and E2F target genes responsible for progression through G1 can then be transcribed. Cyclin D-CDK4 complexes are major integrators of mitogenic and antimitogenic signals.
CDK4 also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. A ternary complex of cyclin D, CDK4 and CDKN1B is required for nuclear translocation and activity of the cyclin D-CDK4 complex. The protein is found in the cytoplasm, the nucleus and the nuclear membrane. Its activity is restricted to the G1-S phase and is controlled by the regulatory D-type cyclins and by the CDK inhibitor p16(INK4a).
The CDK4 gene belongs to the HGNC groups of cyclin dependent kinases and microRNA protein coding host genes. The protein is a member of the protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily, and is highly similar to the products of S. cerevisiae cdc28 and S. pombe cdc2. Mutations in CDK4, D-type cyclins, p16(INK4a) and Rb have all been associated with tumorigenesis in a variety of cancers. Multiple polyadenylation sites have been reported for the gene. Mouse and rat both carry a Cdk4 ortholog.
CDK4 is a catalytic subunit that is important for G1 progression, making it central to studies of the G1/S transition.
Mutations in CDK4, D-type cyclins, p16(INK4a) and Rb are associated with tumorigenesis in a variety of cancers.
Cyclin D-CDK4 phosphorylates RB1, releasing E2F and enabling transcription of target genes that drive G1 progression.
CDK4 activity is controlled by D-type cyclins and p16(INK4a), and cyclin D/CDK4/CDKN1B complexes govern its nuclear translocation.
CDK4 is the catalytic subunit of cyclin D-CDK4 complexes. It phosphorylates RB1 and other retinoblastoma family proteins, which releases E2F and permits transcription of genes needed for G1 progression. It also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity.
The approved HGNC name is cyclin dependent kinase 4, and UniProt lists the protein as cyclin-dependent kinase 4. The alias PSK-J3 is also used. The enzyme carries EC number 2.7.11.22, and the gene is also classed as a microRNA protein coding host gene.
CDK4 is highly similar to yeast cdc28 and cdc2, and mouse and rat each have a Cdk4 ortholog. Mutations in CDK4 and related proteins, including D-type cyclins, p16(INK4a) and Rb, are associated with tumorigenesis in many cancers. Check the datasheet of any product for its validated reactivity.
Other cyclin-dependent kinases and CDK inhibitors that act alongside CDK4 in cell-cycle control.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P11802; product specifications from Assay Genie datasheets.