Gene expression regulation by CDK12: a versatile kinase in cancer with functions beyond CTD phosphorylation

Seung Hyuk Choi1, Seongjae Kim2, Katherine A Jones3

  • 1Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA. sechoi@salk.edu.

Insights

Cyclin-dependent kinase 12 (CDK12) regulates gene expression and is crucial in preventing genome instability in human cancers. Loss of CDK12 function is linked to cancer development, making it a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • Cyclin-dependent kinases (CDKs) are key regulators of cell cycle and gene expression.
  • CDK12, a serine/threonine kinase, has diverse roles in gene expression and tumorigenesis.
  • CDK12 mutations are prevalent in human tumors, leading to genomic instability.

Purpose of the Study:

  • To discuss the multifaceted roles of CDK12 in gene expression regulation.
  • To highlight CDK12's functions in cellular processes beyond transcription elongation.
  • To emphasize CDK12 as a potential therapeutic target for human cancer.

Main Methods:

  • Review of recent studies on CDK12 function and its role in cancer.
  • Analysis of CDK12's involvement in transcription, splicing, and translation.
  • Examination of the consequences of CDK12 loss-of-function mutations.

Main Results:

  • CDK12 regulates transcription elongation, termination, mRNA splicing, and translation.
  • Loss of CDK12 function impairs DNA damage response (DDR) gene expression.
  • Defective DDR gene expression due to CDK12 loss results in genome instability.

Conclusions:

  • CDK12 plays critical roles in maintaining genome stability through regulation of gene expression.
  • Altered CDK12 function contributes to human tumorigenesis.
  • CDK12 represents a promising therapeutic target for cancer treatment.

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