The amino terminus of Smads permits transcriptional specificity

被引:12
作者
Fortuno, ES [1 ]
LeSueur, JA [1 ]
Graff, JM [1 ]
机构
[1] Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX 75390 USA
关键词
Smads; FAST-1; transforming growth factor-beta; Xenopus laevis; transcription;
D O I
10.1006/dbio.2000.0111
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Smad proteins transduce transforming growth factor-beta signals from the cell surface to the nucleus, regulating a variety of physiologic processes. In the nucleus, Smads control gene expression by binding to both DNA and transcription factors. Individual Smads regulate distinct subsets of target genes. The key residues important for this specificity are thought to reside in the carboxyl-terminal MH2 domain. To further examine Smad specificity in vivo, we undertook structure-function studies in Xenopus laevis embryos and found that truncated Smads containing the MH2 domain activate gene transcription. A striking finding revealed by the in vivo analyses was that the functional truncated Smads all behaved identically and had lost wild-type specificity. For most Smads, wild-type activity required the presence of an MH1 domain, either in cis or in trans. Of note, even heterologous MH1 domains could restore wild-type signaling specificity to effector MH2 domains. We found a possible mechanism to account for these observations, as Smad MH1 domains altered the binding of pathway-specific transcription factors to the MH2 domain. Thus, Smad MH1 domains are important to the regulation of transcriptional specificity. (C) 2001 Academic Press.
引用
收藏
页码:110 / 124
页数:15
相关论文
共 79 条
[1]   A novel mesoderm inducer, Madr2 functions in the activin signal transduction pathway [J].
Baker, JC ;
Harland, RM .
GENES & DEVELOPMENT, 1996, 10 (15) :1880-1889
[2]   Smad4 and FAST-1 in the assembly of activin-responsive factor [J].
Chen, X ;
Weisberg, E ;
Fridmacher, V ;
Watanabe, M ;
Naco, G ;
Whitman, M .
NATURE, 1997, 389 (6646) :85-89
[3]   A transcriptional partner for MAD proteins in TGF-beta signalling [J].
Chen, X ;
Rubock, MJ ;
Whitman, M .
NATURE, 1996, 383 (6602) :691-696
[4]   Smad8 mediates the signaling of the receptor serine kinase [J].
Chen, Y ;
Bhushan, A ;
Vale, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (24) :12938-12943
[5]   Determinants of specificity in TGF-β signal transduction [J].
Chen, YG ;
Hata, A ;
Lo, RS ;
Wotton, D ;
Shi, YG ;
Pavletich, N ;
Massagué, J .
GENES & DEVELOPMENT, 1998, 12 (14) :2144-2152
[6]   THE 2-HYBRID SYSTEM - A METHOD TO IDENTIFY AND CLONE GENES FOR PROTEINS THAT INTERACT WITH A PROTEIN OF INTEREST [J].
CHIEN, CT ;
BARTEL, PL ;
STERNGLANZ, R ;
FIELDS, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (21) :9578-9582
[7]   Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene [J].
Dennler, S ;
Itoh, S ;
Vivien, D ;
ten Dijke, P ;
Huet, S ;
Gauthier, JM .
EMBO JOURNAL, 1998, 17 (11) :3091-3100
[8]   MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma [J].
Eppert, K ;
Scherer, SW ;
Ozcelik, H ;
Pirone, R ;
Hoodless, P ;
Kim, H ;
Tsui, LC ;
Bapat, B ;
Gallinger, S ;
Andrulis, IL ;
Thomsen, GH ;
Wrana, JL ;
Attisano, L .
CELL, 1996, 86 (04) :543-552
[9]  
Germain S, 2000, GENE DEV, V14, P435
[10]   Xenopus Mad proteins transduce distinct subsets of signals for the TGF beta superfamily [J].
Graff, JM ;
Bansal, A ;
Melton, DA .
CELL, 1996, 85 (04) :479-487