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CDK12 Activity-Dependent Phosphorylation Events in Human Cells.

Publication ,  Journal Article
Bartkowiak, B; Yan, CM; Soderblom, EJ; Greenleaf, AL
Published in: Biomolecules
October 22, 2019

We asked whether the C-terminal repeat domain (CTD) kinase, CDK12/CyclinK, phosphorylates substrates in addition to the CTD of RPB1, using our CDK12analog-sensitive HeLa cell line to investigate CDK12 activity-dependent phosphorylation events in human cells. Characterizing the phospho-proteome before and after selective inhibition of CDK12 activity by the analog 1-NM-PP1, we identified 5,644 distinct phospho-peptides, among which were 50 whose average relative amount decreased more than 2-fold after 30 min of inhibition (none of these derived from RPB1). Half of the phospho-peptides actually showed >3-fold decreases, and a dozen showed decreases of 5-fold or more. As might be expected, the 40 proteins that gave rise to the 50 affected phospho-peptides mostly function in processes that have been linked to CDK12, such as transcription and RNA processing. However, the results also suggest roles for CDK12 in other events, notably mRNA nuclear export, cell differentiation and mitosis. While a number of the more-affected sites resemble the CTD in amino acid sequence and are likely direct CDK12 substrates, other highly-affected sites are not CTD-like, and their decreased phosphorylation may be a secondary (downstream) effect of CDK12 inhibition.

Duke Scholars

Published In

Biomolecules

DOI

EISSN

2218-273X

Publication Date

October 22, 2019

Volume

9

Issue

10

Location

Switzerland

Related Subject Headings

  • Protein Kinase Inhibitors
  • Phosphorylation
  • Peptides
  • Humans
  • Hela Cells
  • HeLa Cells
  • Cyclin-Dependent Kinases
  • 3206 Medical biotechnology
  • 3102 Bioinformatics and computational biology
  • 3101 Biochemistry and cell biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bartkowiak, B., Yan, C. M., Soderblom, E. J., & Greenleaf, A. L. (2019). CDK12 Activity-Dependent Phosphorylation Events in Human Cells. Biomolecules, 9(10). https://doi.org/10.3390/biom9100634
Bartkowiak, Bartlomiej, Christopher M. Yan, Erik J. Soderblom, and Arno L. Greenleaf. “CDK12 Activity-Dependent Phosphorylation Events in Human Cells.Biomolecules 9, no. 10 (October 22, 2019). https://doi.org/10.3390/biom9100634.
Bartkowiak B, Yan CM, Soderblom EJ, Greenleaf AL. CDK12 Activity-Dependent Phosphorylation Events in Human Cells. Biomolecules. 2019 Oct 22;9(10).
Bartkowiak, Bartlomiej, et al. “CDK12 Activity-Dependent Phosphorylation Events in Human Cells.Biomolecules, vol. 9, no. 10, Oct. 2019. Pubmed, doi:10.3390/biom9100634.
Bartkowiak B, Yan CM, Soderblom EJ, Greenleaf AL. CDK12 Activity-Dependent Phosphorylation Events in Human Cells. Biomolecules. 2019 Oct 22;9(10).

Published In

Biomolecules

DOI

EISSN

2218-273X

Publication Date

October 22, 2019

Volume

9

Issue

10

Location

Switzerland

Related Subject Headings

  • Protein Kinase Inhibitors
  • Phosphorylation
  • Peptides
  • Humans
  • Hela Cells
  • HeLa Cells
  • Cyclin-Dependent Kinases
  • 3206 Medical biotechnology
  • 3102 Bioinformatics and computational biology
  • 3101 Biochemistry and cell biology