Protein Kinase Cθ Modulates Nuclear Receptor-Corepressor Interaction during T Cell Activation

Abstract

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.