Lam Eric, Pareek Tej K, Letterio John J
a Department of Pediatrics; Division of Pediatric Hematology/Oncology; University Hospitals Rainbow Babies & Children's Hospital Center; The Angie Fowler Adolescent & Young Adult Cancer Institute; The Case Comprehensive Cancer Center ; Case Western Reserve University ; Cleveland , OH USA.
Cell Cycle. 2015;14(8):1327-36. doi: 10.4161/15384101.2014.987621.
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.
细胞周期蛋白依赖性激酶5（Cdk5）是丝氨酸/苏氨酸细胞周期蛋白依赖性蛋白激酶家族中的一个独特成员。我们之前证明，小鼠中Cdk5基因表达的破坏会损害T细胞功能，并改善T细胞介导的神经炎症。在这里，我们表明，Cdk5通过在丝氨酸残基861处对mSin3a蛋白进行特异性磷酸化，损害组蛋白脱乙酰基酶1（HDAC1）对基因转录的抑制作用，从而在T细胞激活过程中调节基因表达。T细胞中Cdk5活性的破坏增强了HDAC活性以及HDAC1/mSin3a复合物与白细胞介素-2（IL-2）启动子的结合，导致IL-2基因表达受到抑制。这些数据表明Cdk5在调节T细胞基因表达以及共抑制因子mSin3a的转录调控中起着重要作用。
