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Updated: Jan 16, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

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Dual Modes of Gene Regulation by CDK12

Yubao Wang1,2, Apoorva Baluapuri2,3,4, Cherubin Manokaran1,2

  • 1Departments of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Biorxiv : the Preprint Server for Biology
|October 3, 2025
PubMed

Insights

CDK12 inhibition downregulates some genes but upregulates others, like MYC. This dual effect in cancer, particularly HER2+ breast cancer, clarifies CDK12

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Gene Regulation

Background:

  • Transcription is regulated by kinases, including Cyclin-Dependent Kinase 12 (CDK12).
  • Kinase inhibition typically leads to gene expression downregulation.

Purpose of the Study:

  • To investigate the complex effects of CDK12 inhibition on gene expression.
  • To elucidate the role of CDK12 in transcriptional control and its implications in cancer.

Main Methods:

  • Analysis of gene expression changes upon CDK12 inhibition.
  • Investigating the impact on transcription elongation and termination.
  • Studying CDK12's role in HER2+ breast cancer models.

Main Results:

  • CDK12 inhibition causes both downregulation of long genes and upregulation of short genes, including MYC and enhancer RNAs.
  • Impaired transcription elongation and increased RNA polymerase II termination/arrest observed in long genes.
  • CDK12 inhibition elevates MYC expression in HER2+ breast cancer, leading to cell lethality.

Conclusions:

  • CDK12 inhibition has dual effects on gene expression, impacting both transcription elongation and termination.
  • The upregulation of specific genes like MYC contributes to the anti-proliferative effects of CDK12 inhibitors.
  • Findings have significant translational implications for cancer therapy, especially in HER2+ breast cancer.

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