Sharp, an inducible cofactor that integrates nuclear receptor repression and activation.
A yeast two-hybrid screen using the conserved carboxyl terminus of the nuclear receptor corepressor SMRT as a bait led to the isolation of a novel human gene termed SHARP (SMRT/HDAC1 Associated Repressor Protein). SHARP is a potent transcriptional repressor whose repression domain (RD) interacts directly with SMRT and at least five members of the NuRD complex including HDAC1 and HDAC2. In addition, SHARP binds to the steroid receptor RNA coactivator SRA via an intrinsic RNA binding domain and suppresses SRA-potentiated steroid receptor transcription activity. Accordingly, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. Surprisingly, the expression of SHARP is itself steroid inducible, suggesting a simple feedback mechanism for attenuation of the hormonal response.
Shi
Y
Y
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
Downes
M
M
Xie
W
W
Kao
H Y
HY
Ordentlich
P
P
Tsai
C C
CC
Hon
M
M
Evans
R M
RM
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D056985:Nuclear Receptor Co-Repressor 2; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D004967:Estrogens; C539130:NCOR2 protein, human; C539131:Ncor2 protein, mouse; D056985:Nuclear Receptor Co-Repressor 2; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C405423:steroid receptor RNA activator; C110550:HDAC1 protein, human; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases