Recombinant Human Cdk12 protein

CDK12 (Cyclin-Dependent Kinase 12) is a serine/threonine kinase belonging to the CDK family, primarily involved in transcriptional regulation and genome stability maintenance. It forms a functional complex with Cyclin K to regulate RNA polymerase II (RNAPII)-mediated transcription elongation, mRNA splicing, and DNA damage response. CDK12 phosphorylates the C-terminal domain (CTD) of RNAPII, influencing the recruitment of factors critical for transcriptional termination and co-transcriptional RNA processing. Unlike other transcription-associated CDKs (e.g., CDK9), CDK12 specifically governs the expression of DNA damage response (DDR) genes, including those in the homologous recombination repair (HRR) pathway (e.g., BRCA1. ATR).

Recombinant CDK12 protein is engineered using heterologous expression systems (e.g., E. coli, mammalian cells) for in vitro studies. Its production enables mechanistic exploration of CDK12-Cyclin K interactions, substrate specificity, and regulatory roles in transcription-coupled DDR. Dysregulation of CDK12 is implicated in cancers, particularly ovarian and prostate cancers, where truncating mutations correlate with HRR deficiency and sensitivity to PARP inhibitors. Recombinant CDK12 is pivotal for screening kinase inhibitors, studying resistance mechanisms in cancer therapy, and deciphering post-translational modifications affecting its activity. Recent studies also highlight its potential as a therapeutic target, given its dual role in transcription and genome stability. However, structural complexity and functional overlap with CDK13 pose challenges in developing selective inhibitors. Research tools like recombinant CDK12 thus bridge gaps in understanding its biology and translational applications.