Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor.
Silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is known to interact with Sin3 and recruit the histone deacetylases (HDACs) that lead to hypoacetylation of histones and transrepression of target transcription factors. Herein, we found that coexpression of SMRT significantly repressed transactivations by activating protein-1 (AP-1), nuclear factor-kappaB (NFkappaB), and serum response factor (SRF) in a dose-dependent manner, but not in the presence of trichostatin A, a specific inhibitor of HDAC. Similarly, coexpression of HDAC1 and mSin3A also showed repressive effects. Consistent with these results, the C-terminal region of SMRT directly interacted with SRF, the AP-1 components c-Jun and c-Fos, and the NFkappaB components p50 and p65, as demonstrated by the yeast and mammalian two hybrid tests as well as the glutathione S-transferase pull down assays. Thus, we concluded that SMRT serves to recruit Sin3/HDACs to SRF, NFkappaB, and AP-1 in vivo and modulate their transactivation.
Lee
S K
SK
Center for Ligand and Transcription, Chonnam National University, Kwangju 500-757, Korea.
Kim
J H
JH
Lee
Y C
YC
Cheong
J
J
Lee
J W
JW
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology*; D026362:Serum Response Factor; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C539130:NCOR2 protein, human; D016328:NF-kappa B; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D012097:Repressor Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D018808:Transcription Factor AP-1; C012589:trichostatin A; D005982:Glutathione Transferase