King's College London

Research portal

RhoBTB1 interacts with ROCKs and inhibits invasion

Research output: Contribution to journalArticle

Raquel B. Haga, Ritu Garg, Francesca Collu, Bárbara Borda D’Agua, Sofia T. Menéndez, Audrey Colomba, Franca Fraternali, Anne J. Ridley

Original languageEnglish
Pages (from-to)2499-2514
Number of pages16
JournalBiochemical Journal
Volume476
Issue number17
DOIs
Publication statusPublished - 13 Sep 2019

King's Authors

Abstract

RhoBTB1 is an atypical Rho GTPase with two BTB domains in addition to its Rho domain. Although most Rho GTPases regulate actin cytoskeletal dynamics, RhoBTB1 is not known to affect cell shape or motility. We report that RhoBTB1 depletion increases prostate cancer cell invasion and induces elongation in Matrigel, a phenotype similar to that induced by depletion of ROCK1 and ROCK2. We demonstrate that RhoBTB1 associates with ROCK1 and ROCK2 and its association with ROCK1 is via its Rho domain. The Rho domain binds to the coiled-coil region of ROCK1 close to its kinase domain. We identify two amino acids within the Rho domain that alter RhoBTB1 association with ROCK1. RhoBTB1 is a substrate for ROCK1, and mutation of putative phosphorylation sites reduces its association with Cullin3, a scaffold for ubiquitin ligases. We propose that RhoBTB1 suppresses cancer cell invasion through interacting with ROCKs, which in turn regulate its association with Cullin3. Via Cullin3, RhoBTB1 has the potential to affect protein degradation.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454