Ishaq Mohammad, DeGray Gerald, Natarajan Ven
Laboratory of Molecular Cell Biology, Science Applications International Corp., National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
J Biol Chem. 2003 Oct 10;278(41):39296-302. doi: 10.1074/jbc.M302767200. Epub 2003 Jul 30.
Transcriptional repression by nuclear receptor corepressors plays a critical role in T cell development. However, the role of these corepressors in T cell activation is poorly understood. We report that T cell activation silenced transcription driven by nuclear receptors retinoic acid receptor, retinoid X receptor, and thyroid hormone receptor and induced silencing mediator of retinoic acid and thyroid hormone receptors (SMRT)-receptor interaction. Whereas the expression of a dominant active mutant of protein kinase C theta(PKC theta) induced strong SMRT-receptor interaction in the absence of T cell activation, a dominant negative mutant of PKC theta decreased the interaction. Loss of PKC theta expression by induction of "RNA interference" resulted in the attenuation of basal and activation-induced SMRT-receptor interaction. We suggest that T cell activation silences nuclear receptor-dependent transactivation in part through PKC theta-dependent enhancement of SMRT-receptor interaction.
核受体共抑制因子介导的转录抑制在T细胞发育中起关键作用。然而，这些共抑制因子在T细胞活化中的作用却鲜为人知。我们发现，T细胞活化会使由核受体视黄酸受体、视黄醇X受体和甲状腺激素受体驱动的转录沉默，并诱导视黄酸和甲状腺激素受体沉默介质（SMRT）与受体的相互作用。在没有T细胞活化的情况下，蛋白激酶Cθ（PKCθ）的显性活性突变体的表达会诱导强烈的SMRT-受体相互作用，而PKCθ的显性负性突变体则会降低这种相互作用。通过“RNA干扰”诱导PKCθ表达缺失会导致基础和活化诱导的SMRT-受体相互作用减弱。我们认为，T细胞活化部分通过PKCθ依赖性增强SMRT-受体相互作用，使核受体依赖性反式激活沉默。
