CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
| |
| Authors: | Yunfan Yang Lei Sun Tala Jinmin Gao Dengwen Li Jun Zhou Min Liu |
| |
| Affiliation: | 1. Tianjin Key Laboratory of Protein Science and Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.; 2. Tianjin Key Laboratory of Medical Epigenetics and Department of Biochemistry, Basic Medical College, Tianjin Medical University, Tianjin, China.; Beatson Institute for Cancer Research Glasgow, United Kingdom, |
| |
| Abstract: | Rho family guanosine triphosphatases (GTPases), such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs), which promote the exchange of GDP for GTP. The precise mechanisms regulating the activation of Rho proteins are not fully understood. Herein, we demonstrate that RhoA activity is regulated by cylindromatosis (CYLD), a deubiquitinase harboring multiple functions. In addition, we find that RhoA-mediated cytoskeletal rearrangement, chromosome separation, and cell polarization are altered in CYLD-depleted cells. Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG). Our data further show that CYLD-mediated deubiquitination of LARG enhances its ability to stimulate the GDP/GTP exchange on RhoA. These data thus identify LARG as a new substrate of CYLD and provide novel insights into the regulation of RhoA activation. Our results also suggest that the LARG-RhoA signaling pathway may play a role in diverse CYLD-mediated cellular events. |
| |
| Keywords: | |
|
|
