CDK12 Activity-Dependent Phosphorylation Events in Human Cells
| Autor: | Christopher M. Yan, Bartlomiej Bartkowiak, Arno L. Greenleaf, Erik J. Soderblom |
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| Rok vydání: | 2019 |
| Předmět: |
mESC undifferentiated state
Cellular differentiation lcsh:QR1-502 XPC TPR RNA polymerase II environment and public health Biochemistry lcsh:Microbiology Article 03 medical and health sciences 0302 clinical medicine Transcription (biology) Humans Phosphorylation Nuclear export signal Protein Kinase Inhibitors Molecular Biology Mitosis 030304 developmental biology 0303 health sciences biology analog-sensitive CTD kinase Chemistry Kinase 1-NM-PP1 Cyclin-Dependent Kinases CTD 3. Good health Cell biology enzymes and coenzymes (carbohydrates) RNA processing nuclear pore mRNA nuclear export 030220 oncology & carcinogenesis biology.protein Peptides transcription HeLa Cells |
| Zdroj: | Biomolecules Volume 9 Issue 10 Biomolecules, Vol 9, Iss 10, p 634 (2019) |
| ISSN: | 2218-273X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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