Role of the essential yeast protein PSU1 in transcriptional enhancement by the ligand-dependent activation function AF-2 of nuclear receptors

被引:32
作者
Gaudon, C [1 ]
Chambon, P [1 ]
Losson, R [1 ]
机构
[1] ULP, Coll France, INSERM, CNRS,Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France
关键词
co-activator; ER alpha; LxxLL motif; MutT domain; RAR alpha;
D O I
10.1093/emboj/18.8.2229
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
Nuclear receptors (NRs) can function as ligand-inducible transregulators in both mammalian and yeast cells, indicating that important features of transcriptional control have been conserved throughout evolution. We report here the isolation and characterization of an essential yeast protein of unknown function, PSU1, which exhibits properties expected for a co-activator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of NRs, PSU1 interacts in a ligand-dependent manner with the LED of several NRs, including retinoic acid (RAR alpha), retinoid X (RXR alpha), thyroid hormone (TR alpha), vitamin D3 (VDR) and oestrogen (ER alpha) receptors, Importantly, both in yeast and in vitro, these interactions require the integrity of the AF-2 activating domain. When tethered to a heterologous DNA-binding domain, PSU1 can activate transcription on its own. By using yeast reporter cells that express PSU1 conditionally, we show that PSU1 is required for transactivation by the AF-2 of ER alpha, Taken together these data suggest that in yeast, PSU1 is involved in ligand-dependent transactivation by NRs, Sequence analysis revealed that in addition to a highly conserved moth found in a family of MutT-related proteins, PSU1 contains several a-helical leucine-rich motifs sharing the consensus sequence LLx Phi L (x, any amino acid; Phi, hydrophobic amino acid) in regions that elicit either transactivation or NR-binding activity.
引用
收藏
页码:2229 / 2240
页数:12
相关论文
共 74 条
[1]   SOLUTION STRUCTURE OF THE MUTT ENZYME, A NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE [J].
ABEYGUNAWARDANA, C ;
WEBER, DJ ;
GITTIS, AG ;
FRICK, DN ;
LIN, J ;
MILLER, AF ;
BESSMAN, MJ ;
MILDVAN, AS .
BIOCHEMISTRY, 1995, 34 (46) :14997-15005
[2]   Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1 [J].
Baur, EV ;
Zechel, C ;
Heery, D ;
Heine, MJS ;
Garnier, JM ;
Vivat, V ;
LeDouarin, B ;
Gronemeyer, H ;
Chambon, P ;
Losson, R .
EMBO JOURNAL, 1996, 15 (01) :110-124
[3]   Interaction of steroid hormone receptors with the transcription initiation complex [J].
Beato, M ;
SanchezPacheco, A .
ENDOCRINE REVIEWS, 1996, 17 (06) :587-609
[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]   The MutT proteins or ''nudix'' hydrolases, a family of versatile, widely distributed, ''housecleaning'' enzymes [J].
Bessman, MJ ;
Frick, DN ;
OHandley, SF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (41) :25059-25062
[6]   Mediator of transcriptional regulation [J].
Bjorklund, S ;
Kim, YJ .
TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (09) :335-337
[7]   A POSITIVE SELECTION FOR MUTANTS LACKING OROTIDINE-5'-PHOSPHATE DECARBOXYLASE ACTIVITY IN YEAST - 5-FLUORO-OROTIC ACID RESISTANCE [J].
BOEKE, JD ;
LACROUTE, F ;
FINK, GR .
MOLECULAR & GENERAL GENETICS, 1984, 197 (02) :345-346
[8]   Molecular basis of agonism and antagonism in the oestrogen receptor [J].
Brzozowski, AM ;
Pike, ACW ;
Dauter, Z ;
Hubbard, RE ;
Bonn, T ;
Engstrom, O ;
Ohman, L ;
Greene, GL ;
Gustafsson, JA ;
Carlquist, M .
NATURE, 1997, 389 (6652) :753-758
[9]  
Burns LG, 1997, BBA-GENE STRUCT EXPR, V1350, P159
[10]   RSC, an essential, abundant chromatin-remodeling complex [J].
Cairns, BR ;
Lorch, Y ;
Li, Y ;
Zhang, MC ;
Lacomis, L ;
ErdjumentBromage, H ;
Tempst, P ;
Du, J ;
Laurent, B ;
Kornberg, RD .
CELL, 1996, 87 (07) :1249-1260