tailieunhanh - Báo cáo khoa học: Post-translational modification of the deubiquitinating enzyme otubain 1 modulates active RhoA levels and susceptibility to Yersinia invasion

Microbial pathogens exploit the ubiquitin system to facilitate infection and manipulate the immune responses of the host. In this study, susceptibility to Yersinia enterocolitica and Yersinia pseudotuberculosis invasion was found to be increased upon overexpression of the deubiquitinating enzyme otubain 1 (OTUB1), a member of the ovarian tumour domain-containing protein family. | ỊFEBS Journal Post-translational modification of the deubiquitinating enzyme otubain 1 modulates active RhoA levels and susceptibility to Yersinia invasion Mariola J. Edelmann Holger B. Kramer Mikael Altun and Benedikt M. Kessler Department of ClinicalMedicine University of Oxford UK Keywords deubiquitinating enzymes otubain 1 phosphorylation RhoA YpkA Correspondence B. M. Kessler Henry Wellcome Building for Molecular Physiology Nuffield Department of ClinicalMedicine University of Oxford Roosevelt Drive Oxford OX3 7BN UK Fax 44 1865 287 787 Tel 44 1865 287 799 E-mail bmk@ Received 24 November 2009 revised 17 March 2010 accepted 29 March 2010 doi Microbial pathogens exploit the ubiquitin system to facilitate infection and manipulate the immune responses of the host. In this study susceptibility to Yersinia enterocolitica and Yersinia pseudotuberculosis invasion was found to be increased upon overexpression of the deubiquitinating enzyme otubain 1 OTUB1 a member of the ovarian tumour domain-containing protein family. Conversely OTUB1 knockdown interfered with Yersinia invasion in HEK293T cells as well as in primary monocytes. This effect was attributed to a modulation of bacterial uptake. We demonstrate that the Yersinia-encoded virulence factor YpkA YopO kinase interacts with a post-translationally modified form of OTUB1 that contains multiple phosphorylation sites. OTUB1 YpkA and the small GTPase ras homologue gene family member A RhoA were found to be part of the same protein complex suggesting that RhoA levels are modulated by OTUB1. Our results show that OTUB1 is able to stabilize active RhoA prior to invasion which is concomitant with an increase in bacterial uptake. This effect is modulated by post-translational modifications of OTUB1 suggesting a new entry point for manipulating Yersinia interactions with the host. Structured digital abstract MINT-7717124 ypkA uniprotkb Q05608 physically interacts MI 0915 with .