USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15 (original) (raw)

“…Third, through their deubiquitylating activities, various DUBs, such as USP7 and USP28, have been reported to regulate the levels and/or activities of various oncogene or tumour suppressor proteins 30,31 . Fourth, DUBs modulate other therapeutically relevant cellular components and processes, such as the UPS (for example, USP14 and UCHL5 (also known as UCH37)) 32 , stem cell renewal (for example, USP16 or USP22) 29,33 , DNA damage response (DDR) and DNA repair (for example, USP1 or USP11) 9 , immunooncology (for example, USP7) 34 or receptor tyrosine kinases (for example, USP8 or USP9X) 35,36 . Consequently, and as described in more detail below, various DUBs are emerging as attractive targets for the development of novel cancer therapies.…”

Section: Dubs In Oncologymentioning

“…1D). Therefore, it seems that the ubiquitination/deubiquitination machinery regulating TrkA may appear as complex as in the case of other receptor tyrosine kinases, such as EGFR and Met, for which many identified DUBs regulate in a direct or indirect way the response to their activation by their cognate ligands (34,41). Additional studies need to be carried out to address the role of other DUBs identified in this work within the NGF-TrkA system.…”

Section: Discussionmentioning

“…We looked for DUBs that could alter TrkA activation kinetics in response to NGF performing a siRNA screen, an approach that has been successfully used by several groups trying to identify DUBs involved in the modulation of signaling cascades triggered by different receptors (33,34). We identified USP36 as a DUB that affected not only TrkA signaling but also ubiquitination.…”

Section: Discussionmentioning

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“…Recent work, focused on this enzyme, has established proof of principle that selective small molecule inhibition amongst the USP family can be achieved [15][16][17][18]. USP9X is one of the most abundant members of the USP family and has been linked with many processes, including centrosome function, chromosome alignment during mitosis, EGF receptor degradation, chemo-sensitisation and circadian rhythms [19][20][21][22][23]. Loss of function mutations in females lead to congenital malformations and intellectual disability [24].…”

Section: Introductionmentioning