A role for Groucho tetramerization in transcriptional repression

被引:108
作者
Chen, GQ [1 ]
Nguyen, PH [1 ]
Courey, AJ [1 ]
机构
[1] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
关键词
D O I
10.1128/MCB.18.12.7259
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
The Drosophila Groucho (Gro) protein is a corepressor required by a number of DNA-binding transcriptional repressors. Comparison of Gro with its homologues in other eukaryotic organisms reveals that Gro contains, in addition to a conserved C-terminal WD repeat domain, a conserved N-terminal domain, which has previously been implicated in transcriptional repression. We determined, via a variety of hydrodynamic measurements as well as protein cross-linking, that native Gro is a tetramer in solution and that tetramerization is mediated by two putative amphipathic alpha-helices (termed leucine zipper-like motifs) found in the N-terminal region, Point mutations in the leucine zipper-like motifs that block tetramerization also block repression by Gro, as assayed in cultured Drosophila cells with Gal4-Gro fusion proteins, Furthermore, the heterologous tetramerization domain from p53 fully substitutes for the Gro tetramerization domain in transcriptional repression. These findings suggest that oligomerization is essential for Gro-mediated repression and that the primary function of the conserved N-terminal domain is to mediate this oligomerization.
引用
收藏
页码:7259 / 7268
页数:10
相关论文
共 54 条
[1]   Drosophila CBP is required for dorsal-dependent twist gene expression [J].
Akimaru, H ;
Hou, DX ;
Ishii, S .
NATURE GENETICS, 1997, 17 (02) :211-214
[2]   Groucho-dependent and -independent repression activities of runt domain proteins [J].
Aronson, BD ;
Fisher, AL ;
Blechman, K ;
Caudy, M ;
Gergen, JP .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (09) :5581-5587
[3]   3D DOMAIN SWAPPING - A MECHANISM FOR OLIGOMER ASSEMBLY [J].
BENNETT, MJ ;
SCHLUNEGGER, MP ;
EISENBERG, D .
PROTEIN SCIENCE, 1995, 4 (12) :2455-2468
[4]   MOLECULAR-WEIGHTS OF PROTEIN MULTIMERS FROM POLYACRYLAMIDE-GEL ELECTROPHORESIS [J].
BRYAN, JK .
ANALYTICAL BIOCHEMISTRY, 1977, 78 (02) :513-519
[5]   MECHANISMS OF EARLY NEUROGENESIS IN DROSOPHILA-MELANOGASTER [J].
CAMPOSORTEGA, JA .
JOURNAL OF NEUROBIOLOGY, 1993, 24 (10) :1305-1327
[6]  
Cantor C. R., 1980, BIOPHYS CHEM, V2, P560
[7]  
Chen JL, 1996, METHOD ENZYMOL, V273, P208
[8]   HIGH-RESOLUTION STRUCTURE OF THE OLIGOMERIZATION DOMAIN OF P53 BY MULTIDIMENSIONAL NMR [J].
CLORE, GM ;
OMICHINSKI, JG ;
SAKAGUCHI, K ;
ZAMBRANO, N ;
SAKAMOTO, H ;
APPELLA, E ;
GRONENBORN, AM .
SCIENCE, 1994, 265 (5170) :386-391
[9]   THE MOUSE SEGMENTATION GENE KR ENCODES A NOVEL BASIC DOMAIN LEUCINE-ZIPPER TRANSCRIPTION FACTOR [J].
CORDES, SP ;
BARSH, GS .
CELL, 1994, 79 (06) :1025-1034
[10]   SYNERGISTIC ACTIVATION BY THE GLUTAMINE-RICH DOMAINS OF HUMAN TRANSCRIPTION FACTOR SP1 [J].
COUREY, AJ ;
HOLTZMAN, DA ;
JACKSON, SP ;
TJIAN, R .
CELL, 1989, 59 (05) :827-836