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Cells 2016, 5(2), 28;

Atypical Rho GTPases of the RhoBTB Subfamily: Roles in Vesicle Trafficking and Tumorigenesis

School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, China
Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Cottingham Road, Hull, East Riding of Yorkshire HU6 7RX, UK
Author to whom correspondence should be addressed.
Academic Editor: Bor Luen Tang
Received: 17 May 2016 / Revised: 7 June 2016 / Accepted: 8 June 2016 / Published: 14 June 2016
(This article belongs to the Special Issue Regulation and Function of Small GTPases)
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RhoBTB proteins constitute a subfamily of atypical Rho GTPases represented in mammals by RhoBTB1, RhoBTB2, and RhoBTB3. Their characteristic feature is a carboxyl terminal extension that harbors two BTB domains capable of assembling cullin 3-dependent ubiquitin ligase complexes. The expression of all three RHOBTB genes has been found reduced or abolished in a variety of tumors. They are considered tumor suppressor genes and recent studies have strengthened their implication in tumorigenesis through regulation of the cell cycle and apoptosis. RhoBTB3 is also involved in retrograde transport from endosomes to the Golgi apparatus. One aspect that makes RhoBTB proteins atypical among the Rho GTPases is their proposed mechanism of activation. No specific guanine nucleotide exchange factors or GTPase activating proteins are known. Instead, RhoBTB might be activated through interaction with other proteins that relieve their auto-inhibited conformation and inactivated through auto-ubiquitination and destruction in the proteasome. In this review we discuss our current knowledge on the molecular mechanisms of action of RhoBTB proteins and the implications for tumorigenesis and other pathologic conditions. View Full-Text
Keywords: cullin; cyclin E; HIFα; Rab9; RhoBTB; tumor suppressor; ubiquitination cullin; cyclin E; HIFα; Rab9; RhoBTB; tumor suppressor; ubiquitination

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Ji, W.; Rivero, F. Atypical Rho GTPases of the RhoBTB Subfamily: Roles in Vesicle Trafficking and Tumorigenesis. Cells 2016, 5, 28.

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