TY - JOUR
T1 - Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-κB, and serum response factor
AU - Lee, Soo Kyung
AU - Kim, Jung Hyun
AU - Lee, Young Chul
AU - Cheong, Jae Hun
AU - Lee, Jae Woon
PY - 2000/4/28
Y1 - 2000/4/28
N2 - 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-κB (NFκB), 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 NFκB 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, NFκB, and AP-1 in vivo and modulate their transactivation.
AB - 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-κB (NFκB), 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 NFκB 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, NFκB, and AP-1 in vivo and modulate their transactivation.
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U2 - 10.1074/jbc.275.17.12470
DO - 10.1074/jbc.275.17.12470
M3 - Article
C2 - 10777532
AN - SCOPUS:0034724681
SN - 0021-9258
VL - 275
SP - 12470
EP - 12474
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 17
ER -