Ligand-dependent nuclear receptor corepressor LCoR functions by histone deacetylase-dependent and -independent mechanisms.
LCoR (ligand-dependent corepressor) is a transcriptional corepressor widely expressed in fetal and adult tissues that is recruited to agonist-bound nuclear receptors through a single LXXLL motif. LCoR binding to estrogen receptor alpha depends in part on residues in the coactivator binding pocket distinct from those bound by TIF-2. Repression by LCoR is abolished by histone deacetylase inhibitor trichostatin A in a receptor-dependent fashion, indicating HDAC-dependent and -independent modes of action. LCoR binds directly to specific HDACs in vitro and in vivo. Moreover, LCoR functions by recruiting C-terminal binding protein corepressors through two consensus binding motifs and colocalizes with CtBPs in the nucleus. LCoR represents a class of corepressor that attenuates agonist-activated nuclear receptor signaling by multiple mechanisms.
Fernandes
Isabelle
I
Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Bastien
Yolande
Y
Wai
Timothy
T
Nygard
Karen
K
Lin
Roberto
R
Cormier
Olivier
O
Lee
Han S
HS
Eng
Frankie
F
Bertos
Nicholas R
NR
Pelletier
Nadine
N
Mader
Sylvie
S
Han
Victor K M
VK
Yang
Xiang-Jiao
XJ
White
John H
JH
D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D004791:Enzyme Inhibitors / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005333:Fetus / Q000502:physiology; D017930:Genes, Reporter; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D017403:In Situ Hybridization; D008024:Ligands; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2; D010920:Placenta / Q000166:cytology / Q000502:physiology; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C472166:LCOR protein, human; D008024:Ligands; C498001:NCOA2 protein, human; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C012589:trichostatin A; D006655:Histone Deacetylases