A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP

Ann Båvner; Lotta Johansson; Gudrun Toresson; Jan-Ake Gustafsson; Eckardt Treuter

doi:10.1093/embo-reports/kvf087

A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP

EMBO Rep. 2002 May;3(5):478-84. doi: 10.1093/embo-reports/kvf087. Epub 2002 Apr 18.

Authors

Ann Båvner¹, Lotta Johansson, Gudrun Toresson, Jan-Ake Gustafsson, Eckardt Treuter

Affiliation

¹ Department of Biosciences at Novum, Karolinska Institutet, S-14157 Huddinge, Sweden.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyltransferases / metabolism
Adenovirus E1A Proteins / genetics
Adenovirus E1A Proteins / metabolism*
Amino Acid Sequence
Animals
COS Cells
Carrier Proteins / metabolism
Cell Cycle Proteins
DNA Mutational Analysis
Gene Expression Regulation* / physiology*
Histones / metabolism
Intracellular Signaling Peptides and Proteins*
Mice
Molecular Sequence Data
Mutation
Nuclear Proteins
Nuclear Receptor Coactivators
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
Repressor Proteins / metabolism*
Sequence Analysis, Protein
Transcription, Genetic
Two-Hybrid System Techniques

Substances

Adenovirus E1A Proteins
Carrier Proteins
Cell Cycle Proteins
EID1 protein, human
Histones
Intracellular Signaling Peptides and Proteins
NCOA6 protein, human
Ncoa6 protein, mouse
Nuclear Proteins
Nuclear Receptor Coactivators
Receptors, Cytoplasmic and Nuclear
Repressor Proteins
nuclear receptor subfamily 0, group B, member 2
Acetyltransferases