Protein kinase C theta modulates nuclear receptor-corepressor interaction during T cell activation.
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.
Ishaq
Mohammad
M
Laboratory of Molecular Cell Biology, Science Applications International Corp., National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. mishaq@nih.gov
DeGray
Gerald
G
Natarajan
Ven
V
D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D020868:Gene Silencing; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D009154:Mutation; D056985:Nuclear Receptor Co-Repressor 2; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D018106:CD28 Antigens; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta