PMID:28416637

Citation	'Audetat, KA, Galbraith, MD, Odell, AT, Lee, T, Pandey, A, Espinosa, JM, Dowell, RD and Taatjes, DJ (2017) A kinase-independent role for CDK19 in p53 response. Mol. Cell. Biol. '
Abstract	The human Mediator complex regulates RNA Polymerase II transcription genome-wide. A general factor that regulates Mediator function is the four-subunit kinase module, which contains either CDK8 or CDK19. Whereas CDK8 is linked to specific signaling cascades and oncogenesis, the cellular roles of its paralog, CDK19, are poorly studied. We discovered that osteosarcoma cells (SJSA) are naturally depleted of CDK8 protein. Whereas stable CDK19 knockdown was tolerated in SJSA cells, proliferation was reduced. Notably, proliferation defects were rescued upon re-expression of wild-type or kinase-dead CDK19. RNA-Seq analyses showed reduced expression of mitotic genes and activation of genes associated with cholesterol metabolism and the p53 pathway in CDK19 knockdown cells. SJSA cells treated with 5-fluorouracil (5-FU), which induces metabolic and genotoxic stress and activates p53, further implicated CDK19 in p53 target gene expression. To better probe the p53 response, SJSA cells (shCDK19 vs. shCTRL) were treated with the p53 activator Nutlin-3. Remarkably, CDK19 was required for SJSA cells to return to a proliferative state following Nutlin-3 treatment, and this effect was kinase-independent. These results implicate CDK19 as a regulator of p53 stress responses and suggest a role for CDK19 in cellular resistance to Nutlin-3.
Links	PubMed Online version:10.1128/MCB.00626-16
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CDK19		GO:0008283: cell proliferation	ECO:0000316:		P		Expression of CDK8 rescues the proliferation defect in shCDK19 cells treated with Nutlin-3.	Missing: with/from CACAO 12754
HUMAN:CDK8		GO:0008283: cell proliferation	ECO:0000316:		P		Expression of CDK8 rescues the proliferation defect in shCDK19 cells treated with Nutlin-3.	Missing: with/from CACAO 12755

References

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