Negative feedback regulation of TGF-β signaling by the SnoN oncoprotein

被引：430

作者：

Stroschein, SL

Wang, W

Zhou, SL

Zhou, Q

Luo, KX

机构：

[1] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

来源：

SCIENCE | 1999年 / 286卷 / 5440期

关键词：

D O I：

10.1126/science.286.5440.771

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR, Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target genes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-beta-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling.

引用

页码：771 / 774

页数：4

共 49 条

[1] T beta RI phosphorylation of Smad2 on Ser(465) and Ser(467) is required for Smad2-Smad4 complex formation and signaling
Abdollah, S
MaciasSilva, M
Tsukazaki, T
Hayashi, H
Attisano, L
Wrana, JL
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (44) : 27678 - 27685
[2] Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression
Alland, L
Muhle, R
Hou, H
Potes, J
Chin, L
SchreiberAgus, N
DePinho, RA
[J]. NATURE, 1997, 387 (6628) : 49 - 55
[3] A novel mesoderm inducer, Madr2 functions in the activin signal transduction pathway
Baker, JC
Harland, RM
[J]. GENES & DEVELOPMENT, 1996, 10 (15) : 1880 - 1889
[4] BOYER PL, 1993, ONCOGENE, V8, P457
[5] Smad4 and FAST-1 in the assembly of activin-responsive factor
Chen, X
Weisberg, E
Fridmacher, V
Watanabe, M
Naco, G
Whitman, M
[J]. NATURE, 1997, 389 (6646) : 85 - 89
[6] A transcriptional partner for MAD proteins in TGF-beta signalling
Chen, X
Rubock, MJ
Whitman, M
[J]. NATURE, 1996, 383 (6602) : 691 - 696
[7] A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAFII110
Cohen, SB
Nicol, R
Stavnezer, E
[J]. ONCOGENE, 1998, 17 (19) : 2505 - 2513
[8] Transformation of hematopoietic cells by the Ski oncoprotein involves repression of retinoic acid receptor signaling
Dahl, R
Kieslinger, M
Beug, H
Hayman, MJ
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (19) : 11187 - 11192
[9] Characterization of functional domains within Smad4/DPC4
deCaestecker, MP
Hemmati, P
LarischBloch, S
Ajmera, R
Roberts, AB
Lechleider, RJ
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) : 13690 - 13696
[10] 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

← 1 2 3 4 5 →