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Abstract
Cyclin-dependent kinase 5 (Cdk5) is a unique member of a family of serine/threonine cyclin-dependent protein kinases. We previously demonstrated disruption of Cdk5 gene expression in mice impairs T-cell function and ameliorates T-cell-mediated neuroinflammation. Here, we show Cdk5 modulates gene expression during T-cell activation by impairing the repression of gene transcription by histone deacetylase 1 (HDAC1) through specific phosphorylation of the mSin3a protein at serine residue 861. Disruption of Cdk5 activity in T-cells enhances HDAC activity and binding of the HDAC1/mSin3a complex to the IL-2 promoter, leading to suppression of IL-2 gene expression. These data point to essential roles for Cdk5 in regulating gene expression in T-cells and transcriptional regulation by the co-repressor mSin3a.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Funding
We would like to acknowledge support from the Jane and Lee Seidman Chair in Pediatric Cancer Innovation and grants from the NIH (5R01HL111682–02 and R01 EY022937-01), Hyundai Hope on Wheels Foundation, and the St. Baldrick's Foundation for Pediatric Cancer Research.