RhoB is stabilized by transforming growth factor beta and antagonizes transcriptional activation.
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 effectors. Among these, the Smads have been extensively studied. However, less attention has been directed toward alternative downstream effectors 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.
Engel
M E
ME
Department of Cell Biology and the Vanderbilt Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-6838, USA.
Datta
P K
PK
Moses
H L
HL
D000818:Animals; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex; D017368:Protein Prenylation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014452:Ubiquitins / Q000378:metabolism; D020743:rhoB GTP-Binding Protein
D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D014452:Ubiquitins; D008156:Luciferases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020743:rhoB GTP-Binding Protein