RhoB is stabilized by transforming growth factor β and antagonizes transcriptional activation

被引：87

作者：

Engel, ME

Datta, PK

Moses, HL

机构：

[1] Vanderbilt Univ, Vanderbilt Canc Ctr, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Cell Biol, Nashville, TN 37232 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1998年 / 273卷 / 16期

关键词：

D O I：

10.1074/jbc.273.16.9921

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：

Transforming growth factor beta (TGF-beta) is the prototype for an evolutionarily conserved superfamily of secreted factors implicated in diverse biological phenomena. The pleiotropic responses to TGF-beta are initiated by a heteromeric receptor complex that binds and phosphorylates downstream effecters. Among these, the Smads have been extensively studied. However, less attention has been directed toward alternative downstream effecters and their participation in TGF-beta signal transduction. We show that TGF-beta promotes accumulation of the labile monomeric GTPase RhoB by antagonizing its normal proteolytic destruction, presumably via the 26 S proteasome. RhoB accumulates in its isoprenylated form. Transient overexpression of wild type RhoB but not its dominant negative mutant RhoB-N19 antagonizes TGF-beta-mediated transcriptional activation. These results suggest a novel mechanism of regulation by TGF-beta and implicate RhoB as a negative regulator of TGF-beta signal transduction.

引用

页码：9921 / 9926

页数：6

共 29 条

[1] ADAMSON P, 1992, J BIOL CHEM, V267, P20033
[2] Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling
Atfi, A
Djelloul, S
Chastre, E
Davis, RR
Gespach, C
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (03) : 1429 - 1432
[3] A WD-DOMAIN PROTEIN THAT IS ASSOCIATED WITH AND PHOSPHORYLATED BY THE TYPE-II TGF-BETA RECEPTOR
CHEN, RH
MIETTINEN, PJ
MARUOKA, EM
CHOY, L
DERYNCK, R
[J]. NATURE, 1995, 377 (6549) : 548 - 552
[4] CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[5] EGF MODULATION OF THE RAS-RELATED RHOB GENE-EXPRESSION IN HUMAN BREAST-CANCER CELL-LINES
DECREMOUX, P
GAUVILLE, C
CLOSSON, V
LINARES, G
CALVO, F
TAVITIAN, A
OLOFSSON, B
[J]. INTERNATIONAL JOURNAL OF CANCER, 1994, 59 (03) : 408 - 415
[6] Differential translocation of Rho family GTPases by lysophosphatidic acid, endothelin-1, and platelet-derived growth factor
Fleming, IN
Elliott, CM
Exton, JH
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (51) : 33067 - 33073
[7] THE RAS-RELATED SMALL GTP-BINDING PROTEIN RHOB IS IMMEDIATE-EARLY INDUCIBLE BY DNA-DAMAGING TREATMENTS
FRITZ, G
KAINA, B
AKTORIES, K
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (42) : 25172 - 25177
[8] TRANSCRIPTIONAL REGULATION BY EXTRACELLULAR SIGNALS - MECHANISMS AND SPECIFICITY
HILL, CS
TREISMAN, R
[J]. CELL, 1995, 80 (02) : 199 - 211
[9] Ubiquitin-dependent protein degradation
Hochstrasser, M
[J]. ANNUAL REVIEW OF GENETICS, 1996, 30 : 405 - 439
[10] JAHNER D, 1991, MOL CELL BIOL, V11, P3682

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