Cdk5 controls IL-2 gene expression via repression of the mSin3a-HDAC complex

Cell Cycle
Eric LamJohn J Letterio

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.

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Citations

Jan 9, 2020·Open Biology·Samanta Sharma, Piotr Sicinski
Apr 30, 2020·Nature Reviews. Immunology·Giulia PetroniLorenzo Galluzzi
Jan 6, 2021·Cancers·Phuong Anh Do, Chang Hoon Lee
Apr 28, 2021·Molecular Reproduction and Development·Sheryl K MunroAnna P Ponnampalam

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Methods Mentioned

BETA
ELISA
transfection
immunoprecipitation
ChIP
acetylation
Assay
Enzyme-Linked Immunosorbent
electrophoresis

Software Mentioned

GraphPad
Prism

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