Human CDK12 and CDK13, multi-tasking CTD kinases for the new millenium

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• CDK12 and CDK13, discovered as nucleotide sequences encoding protein kinases, are related to cell cycle CDKs.
• Both proteins function as CTD (C-terminal repeat domain of POLR2A) kinases, forming heterodimers with a Cyclin K subunit.

Purpose of the Study:

• This review summarizes current research on CDK12 and CDK13, evaluating findings and placing them in context.
• It aims to highlight the distinct roles of CDK12 and CDK13 and identify future research directions, particularly in cancer biology.

Main Methods:

• Literature review of studies on CDK12 and CDK13.
• Analysis of the functional roles of these kinases in gene expression and genome stability.

Main Results:

• CDK12 plays critical roles in gene expression, RNA processing, and genome stability through CTD phosphorylation of transcribing RNAPII.
• CDK13 is functionally distinct from CDK12, involved in gene expression with likely undiscovered roles.
• CDK12 functions as a tumor suppressor in ovarian and prostate cancers.

Conclusions:

• Understanding of CDK12 and CDK13 is maturing, but further research is needed.
• Future research should focus on elucidating how the loss of CDK12 and CDK13 contributes to cancer development.
• Investigating therapeutic interventions targeting these pathways is a key future challenge.