Engel M E, Datta P K, Moses H L
Department of Cell Biology and the Vanderbilt Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-6838, USA.
J Biol Chem. 1998 Apr 17;273(16):9921-6. doi: 10.1074/jbc.273.16.9921.
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.
转化生长因子β（TGF-β）是一个在进化上保守的分泌因子超家族的原型，该超家族涉及多种生物学现象。对TGF-β的多效性反应由一个异源三聚体受体复合物启动，该复合物结合并磷酸化下游效应物。其中，Smads蛋白已得到广泛研究。然而，对其他下游效应物及其在TGF-β信号转导中的参与关注较少。我们发现，TGF-β可能通过26S蛋白酶体拮抗不稳定的单体GTP酶RhoB的正常蛋白水解破坏，从而促进其积累。RhoB以其异戊二烯化形式积累。野生型RhoB的瞬时过表达而非其显性负性突变体RhoB-N19可拮抗TGF-β介导的转录激活。这些结果提示了一种TGF-β调节的新机制，并表明RhoB是TGF-β信号转导负调节因子。
