ACTIVATION FUNCTION-2 (AF-2) OF RETINOIC ACID RECEPTOR AND 9-CIS RETINOIC ACID RECEPTOR - PRESENCE OF A CONSERVED AUTONOMOUS CONSTITUTIVE ACTIVATING DOMAIN AND INFLUENCE OF THE NATURE OF THE RESPONSE ELEMENT ON AF-2 ACTIVITY

被引:329
作者
DURAND, B [1 ]
SAUNDERS, M [1 ]
GAUDON, C [1 ]
ROY, B [1 ]
LOSSON, R [1 ]
CHAMBON, P [1 ]
机构
[1] UNIV STRASBOURG 1, COLL FRANCE,INST GENET & BIOL MOLEC & CELLULAIRE, CNRS,INSERM, F-67404 ILLKIRCH GRAFFENSTADEN, FRANCE
关键词
DOMINANT NEGATIVE MUTANT; LIGAND-INDUCIBLE TRANSACTIVATION FUNCTION; NUCLEAR RECEPTORS; RESPONSE ELEMENT; RETINOID RECEPTORS;
D O I
10.1002/j.1460-2075.1994.tb06872.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A motif essential for the transcriptional activation function 2 (AF-2) present in the E region of retinoic acid receptor (RAR) alpha and 9-cis retinoic acid receptor (RXR) alpha has been characterized as an amphipathic alpha-helix whose main features are conserved between transcriptionally active members of the nuclear receptor superfamily. This conserved motif, which can activate autonomously in the absence of ligand in animal and yeast cells, can be swapped between nuclear receptors without affecting the ligand dependency for activation of transcription, thus indicating that a ligand-dependent conformational change is necessary to reveal the AF-2 activation potential within the E region of the nuclear receptor. Interestingly, we show that the precise nature of the direct repeat response element to which RAR/RXR heterodimers are bound can affect the activity of the AF-2s of the heterodimeric partners, as well as the relative efficiency with which all-trans and 9-cis retinoic acids activate the RAR partner.
引用
收藏
页码:5370 / 5382
页数:13
相关论文
共 75 条
[1]   THE CONSERVED 9TH C-TERMINAL HEPTAD IN THYROID-HORMONE AND RETINOIC ACID RECEPTORS MEDIATES DIVERSE RESPONSES BY AFFECTING HETERODIMER BUT NOT HOMODIMER FORMATION [J].
AUFLIEGNER, M ;
HELMER, E ;
CASANOVA, J ;
RAAKA, BM ;
SAMUELS, HH .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (09) :5725-5737
[2]   CHARACTERIZATION OF THE LIGAND-DEPENDENT TRANSACTIVATION DOMAIN OF THYROID-HORMONE RECEPTOR [J].
BARETTINO, D ;
RUIZ, MDMV ;
STUNNENBERG, HG .
EMBO JOURNAL, 1994, 13 (13) :3039-3049
[3]   UNLIGANDED T3R, BUT NOT ITS ONCOGENIC VARIANT, V-ERBA, SUPPRESSES RAR-DEPENDENT TRANSACTIVATION BY TITRATING OUT RXR [J].
BARETTINO, D ;
BUGGE, TH ;
BARTUNEK, P ;
RUIZ, MDMV ;
SONNTAGBUCK, V ;
BEUG, H ;
ZENKE, M ;
STUNNENBERG, HG .
EMBO JOURNAL, 1993, 12 (04) :1343-1354
[4]   ROLE OF THE 2 ACTIVATING DOMAINS OF THE ESTROGEN-RECEPTOR IN THE CELL-TYPE AND PROMOTER-CONTEXT DEPENDENT AGONISTIC ACTIVITY OF THE ANTIESTROGEN 4-HYDROXYTAMOXIFEN [J].
BERRY, M ;
METZGER, D ;
CHAMBON, P .
EMBO JOURNAL, 1990, 9 (09) :2811-2818
[5]   THYROID-HORMONE RECEPTOR TRANSCRIPTIONAL ACTIVITY IS POTENTIALLY AUTOREGULATED BY TRUNCATED FORMS OF THE RECEPTOR [J].
BIGLER, J ;
HOKANSON, W ;
EISENMAN, RN .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (05) :2406-2417
[6]  
BLOMHOFF RB, 1994, VITAMIN A HLTH DISEA
[7]  
Chambon Pierre, 1994, Seminars in Cell Biology, V5, P115, DOI 10.1006/scel.1994.1015
[8]  
COONEY AJ, 1993, J BIOL CHEM, V268, P4152
[9]   CRITICAL STRUCTURAL ELEMENTS OF THE VP16 TRANSCRIPTIONAL ACTIVATION DOMAIN [J].
CRESS, WD ;
TRIEZENBERG, SJ .
SCIENCE, 1991, 251 (4989) :87-90
[10]   RETINOIC ACID RECEPTOR BELONGS TO A SUBCLASS OF NUCLEAR RECEPTORS THAT DO NOT FORM DOCKING COMPLEXES WITH HSP90 [J].
DALMAN, FC ;
STURZENBECKER, LJ ;
LEVIN, AA ;
LUCAS, DA ;
PERDEW, GH ;
PETKOVITCH, M ;
CHAMBON, P ;
GRIPPO, JF ;
PRATT, WB .
BIOCHEMISTRY, 1991, 30 (22) :5605-5608