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The coactivator TIF2 contains three nuclear receptor‐binding motifs and mediates transactivation through CBP binding‐dependent and ‐independent pathways
Author(s) -
Voegel Johannes J.,
Heine Matthias J.S.,
Tini Marc,
Vivat Valérie,
Chambon Pierre,
Gronemeyer Hinrich
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.2.507
Subject(s) - transactivation , biology , coactivator , nuclear receptor , nuclear receptor coactivator 3 , nuclear receptor coactivator 2 , plasma protein binding , binding site , nuclear receptor coactivator 1 , microbiology and biotechnology , receptor , dna binding protein , transcription factor , genetics , gene
The nuclear receptor (NR) coactivator TIF2 possesses a single NR interaction domain (NID) and two autonomous activation domains, AD1 and AD2. The TIF2 NID is composed of three NR‐interacting modules each containing the NR box motif LxxLL. Mutation of boxes I, II and III abrogates TIF2–NR interaction and stimulation, in transfected cells, of the ligand‐induced activation function‐2 (AF‐2) present in the ligand‐binding domains (LBDs) of several NRs. The presence of an intact NR interaction module II in the NID is sufficient for both efficient interaction with NR holo‐LBDs and stimulation of AF‐2 activity. Modules I and III are poorly efficient on their own, but synergistically can promote interaction with NR holo‐LBDs and AF‐2 stimulation. TIF2 AD1 activity appears to be mediated through CBP, as AD1 could not be separated mutationally from the CBP interaction domain. In contrast, TIF2 AD2 activity apparently does not involve interaction with CBP. TIF2 exhibited the characteristics expected for a bona fide NR coactivator, in both mammalian and yeast cells. Moreover, in mammalian cells, a peptide encompassing the TIF2 NID inhibited the ligand‐induced AF‐2 activity of several NRs, indicating that NR AF‐2 activity is either mediated by endogenous TIF2 or by coactivators recognizing a similar surface on NR holo‐LBDs.