The CDK5RAP3 gene is located on chromosome 17q21.32 in humans . It encodes a protein that consists of 526 amino acids and has a molecular mass of approximately 59 kDa . The protein is produced in E. coli as a single, non-glycosylated polypeptide chain and is fused to a 20 amino acid His-tag at the N-terminus for purification purposes .
CDK5RAP3 is known to interact with the cyclin-dependent kinase 5 (CDK5) regulatory subunit, CDK5R1, and acts as a potential regulator of CDK5 activity . CDK5 is a neuronal CDC2-like kinase involved in the regulation of neuronal differentiation. It is composed of a catalytic subunit, CDK5, and an activating subunit, p25NCK5A .
The protein has been reported to function in several signaling pathways, including those governing transcriptional regulation and cell cycle progression . It negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation . Additionally, CDK5RAP3 is involved in the mitotic G2/M transition checkpoint and the mitotic G2 DNA damage checkpoint .
CDK5RAP3 has been implicated in tumorigenesis and metastasis . It is considered a probable tumor suppressor, initially identified as a CDK5R1 interactor controlling cell proliferation . Through its interaction with CDKN2A/ARF and MDM2, CDK5RAP3 may induce MDM2-dependent p53/TP53 ubiquitination, stabilization, and activation in the nucleus, thereby promoting G1 cell cycle arrest and inhibition of cell proliferation .