TGF-β signaling by Smad proteins

被引:230
作者
Miyazono, K [1 ]
机构
[1] Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Toshima Ku, Tokyo 1708455, Japan
基金
日本学术振兴会;
关键词
TGF-beta; BMP; adenoviral expression vector; Smad; transcription;
D O I
10.1016/S1359-6101(99)00025-8
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
Smads are signal transducers for the members of the transforming growth factor-p (TGF-P) superfamily. Bone morphogenetic proteins (BMPs) and their receptors induce differentiation of C2C12 cells into osteoblast-like cells. Using an adenoviral expression vector system, we showed that receptor-regulated Smads (R-Smads) activated by BMPs can induce the differentiation of C2C12 cells. Inhibitory Smads (I-Smads) interfere with the osteoblast differentiation of C2C12 cells by preventing the nuclear translocation of R-Smads. After translocation into the nucleus, Smad oligomers regulate the transcription of target genes through binding to DNA directly, interaction with other DNA binding proteins, and recruitment of transcriptional co-activators or co-repressors. Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:15 / 22
页数:8
相关论文
共 42 条
  • [1] c-Ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interaction with Smads
    Akiyoshi, S
    Inoue, H
    Hanai, J
    Kusanagi, K
    Nemoto, N
    Miyazono, K
    Kawabata, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (49) : 35269 - 35277
  • [2] HUMAN OSTEOGENIC PROTEIN-1 INDUCES BOTH CHONDROBLASTIC AND OSTEOBLASTIC DIFFERENTIATION OF OSTEOPROGENITOR CELLS DERIVED FROM NEWBORN RAT CALVARIA
    ASAHINA, I
    SAMPATH, TK
    NISHIMURA, I
    HAUSCHKA, PV
    [J]. JOURNAL OF CELL BIOLOGY, 1993, 123 (04) : 921 - 933
  • [3] Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene
    Dennler, S
    Itoh, S
    Vivien, D
    ten Dijke, P
    Huet, S
    Gauthier, JM
    [J]. EMBO JOURNAL, 1998, 17 (11) : 3091 - 3100
  • [4] A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3
    Dennler, S
    Huet, S
    Gauthier, JM
    [J]. ONCOGENE, 1999, 18 (08) : 1643 - 1648
  • [5] Ebisawa T, 1999, J CELL SCI, V112, P3519
  • [6] The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation
    Feng, XH
    Zhang, Y
    Wu, RY
    Derynck, R
    [J]. GENES & DEVELOPMENT, 1998, 12 (14) : 2153 - 2163
  • [7] Roles of bone morphogenetic protein type I receptors and smad proteins in osteoblast and chondroblast differentiation
    Fujii, M
    Takeda, K
    Imamura, T
    Aoki, H
    Sampath, TK
    Enomoto, S
    Kawabata, M
    Kato, M
    Ichijo, H
    Miyazono, K
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (11) : 3801 - 3813
  • [8] Interaction and functional cooperation of PEBP2/CBF with Smads -: Synergistic induction of the immunoglobulin germline Cα promoter
    Hanai, J
    Chen, LF
    Kanno, T
    Ohtani-Fujita, N
    Kim, WY
    Guo, WH
    Imamura, T
    Ishidou, Y
    Fukuchi, M
    Shi, MJ
    Stavnezer, J
    Kawabata, M
    Miyazono, K
    Ito, Y
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (44) : 31577 - 31582
  • [9] TGF-beta signalling from cell membrane to nucleus through SMAD proteins
    Heldin, CH
    Miyazono, K
    tenDijke, P
    [J]. NATURE, 1997, 390 (6659) : 465 - 471
  • [10] Transforming growth factor β1 induces nuclear export of inhibitory Smad7
    Itoh, S
    Landström, M
    Hermansson, A
    Itoh, F
    Heldin, CH
    Heldin, NE
    ten Dijke, P
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) : 29195 - 29201