RhoB Is Stabilized by Transforming Growth Factor β and Antagonizes Transcriptional Activation*
- From the Department of Cell Biology and the Vanderbilt Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-6838
Abstract
Transforming growth factor β (TGF-β) is the prototype for an evolutionarily conserved superfamily of secreted factors implicated in diverse biological phenomena. The pleiotropic responses to TGF-β are initiated by a heteromeric receptor complex that binds and phosphorylates downstream effectors. Among these, the Smads have been extensively studied. However, less attention has been directed toward alternative downstream effectors and their participation in TGF-β signal transduction. We show that TGF-β 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-β-mediated transcriptional activation. These results suggest a novel mechanism of regulation by TGF-β and implicate RhoB as a negative regulator of TGF-β signal transduction.
Footnotes
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↵* This work was supported by National Institutes of Health Grants CA42572 and CA48799.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Vanderbilt Cancer Center, 649 MRBII, Nashville, TN 37232-6838. Tel.: 615-936-1786; Fax: 615-936-1790; E-mail: hal.moses{at}MCmail.vanderbilt.edu.
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↵1 The abbreviations used are: TGF-β, transforming growth factor β; TβRI, transmembrane serine/threonine kinase receptor type I; TβRII, transmembrane serine/threonine kinase receptor type II; SAPK/JNK, stress-activated protein kinase/c-Jun N-terminal kinase; DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; HA, hemagglutinin; LLnL, leucinyl-leucinyl-norleucinal; PBS, phosphate-buffered saline; PAGE, polyacrylamide gel electrophoresis; PCR, polymerase chain reaction; RT, reverse transcription; bp, base pair; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Tricine,N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine; NTA, nitrilotriacetic acid.
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- Received January 5, 1998.
- Revision received February 20, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
