A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP.
SHP (short heterodimer partner, NROB2) is an atypical orphan member of the mammalian nuclear receptor family that consists only of a putative ligand-binding domain and thus cannot bind DNA. Instead, SHP acts as a transcriptional coregulator by inhibiting the activity of various nuclear receptors (downstream targets) via occupation of the coactivator-binding surface and active repression. However, repression mechanisms have remained elusive and may involve coinhibitory factors (upstream targets) distinct from known nuclear receptor corepressors. Here, we describe the isolation of mouse E1A-like inhibitor of differentiation 1 (EID1) as a candidate coinhibitor for SHP. We characterize the interactions between SHP and EID1 and identify two repression-defective SHP mutations that have lost the ability to bind EID1. We suggest histone acetyltransferases and histones as targets for EID1 action and propose that SHP inhibition of transcription involves EID1 antagonism of CBP/p300-dependent coactivator functions.
Båvner
Ann
A
Department of Biosciences at Novum, Karolinska Institutet, S-14157 Huddinge, Sweden.
Johansson
Lotta
L
Toresson
Gudrun
G
Gustafsson
Jan-Ake
JA
Treuter
Eckardt
E
D000123:Acetyltransferases / Q000378:metabolism; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C416925:EID1 protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; C405683:Ncoa6 protein, mouse; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C099713:nuclear receptor subfamily 0, group B, member 2; D000123:Acetyltransferases