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Ras–GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease

Oncogene volume 20, pages 3869–3879 (2001)Cite this article

Abstract

Degradation of cellular proteins through ubiquitination is a fundamental strategy for regulating biological pathways. De-ubiquitination, i.e. the removal of ubiquitin from proteins and peptides to which ubiquitin is attached, is catalyzed by processing proteases known as de-ubiquitinating enzymes. We are studying the biology of a family of de-ubiquitinating enzymes, the mammalian ubiquitin-specific proteases (USPs), some of which appear to play a role in growth control. Given the fact that the modes of regulation of USPs and of their substrate specificity are poorly understood, we decided to attempt the identification of USP interacting proteins. Using the yeast two-hybrid system (2HS), we have isolated a cDNA clone whose product specifically interacts with USP10 but not with other USP baits tested. The isolated clone encodes a protein known to interact with the Ras-GTPase activating protein (G3BP). This interaction was further confirmed by performing a 2HS with G3BP, which led to the isolation of USP10 encoding cDNAs. We validated the interaction between the two proteins by performing in vitro binding assays and immunoprecipitations in human cells. G3BP does not appear to be a substrate of USP10; it rather inhibits the ability of USP10 to disassemble ubiquitin chains. The USP10/G3BP complex appears to co-immunoprecipitate with ubiquitinated species that could be substrates of USP10.

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Acknowledgements

We thank Barbara Verducci for technical assistance with polyclonal antibodies production and purification and Daniele Piccini for production of monoclonal antibodies. We thank Jorge Dominguez for his assistance with production of recombinant protein in insect cells and Alexandra Charlesworth for DNA sequencing. We would like to thank: Isabel Chou for providing us the yeast two-hybrid mouse cDNA library and the pV16-USP4 clone, Pier Paolo Di Fiore and Kristian Helin for cDNA libraries. We also thank Francesca Fiore and Ciro Mercurio for scientific support and suggestions. We acknowledge support from the Associazione Italiana per la Ricerca sul Cancro (AIRC and the Fondazione Italiana per la Ricerca sul Cancro (FIRC), the Italian Ministry of Health, Telethon and CNR PF Biotecnologie.

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  1. Chiara Soncini

    Present address: Pharmacia Corporation, Discovery Research Oncology, Nerviano, 20014, Italy

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  1. Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, Milan, 20141, Italy

    Chiara Soncini, Ingrid Berdo & Giulio Draetta

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  1. Chiara Soncini
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  2. Ingrid Berdo
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  3. Giulio Draetta
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Correspondence to Giulio Draetta.

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Soncini, C., Berdo, I. & Draetta, G. Ras–GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease. Oncogene 20, 3869–3879 (2001). https://doi.org/10.1038/sj.onc.1204553

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