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Cell Biochem Biophys. 2013 Sep;67(1):25-43. doi: 10.1007/s12013-013-9635-3.

Deubiquitylating enzymes and DNA damage response pathways.

Author information

1
MISSION Therapeutics Ltd, Babraham Research Campus, Cambridge, CB22 3AT, UK. xjacq@missiontherapeutics.com

Abstract

Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention. The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways. Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients.

PMID:
23712866
PMCID:
PMC3756857
DOI:
10.1007/s12013-013-9635-3
[Indexed for MEDLINE]
Free PMC Article

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