TY - JOUR
T1 - Functional analysis of deubiquitylating enzymes in tumorigenesis and development
AU - Cheng, Ji
AU - Guo, Jianping
AU - North, Brian J.
AU - Wang, Bin
AU - Cui, Chun Ping
AU - Li, Hongchang
AU - Tao, Kaixiong
AU - Zhang, Lingqiang
AU - Wei, W.
N1 - Funding Information:
The authors sincerely apologize to all those colleagues whose important work was not cited in this paper due to space limitations. They thank the members of Wei laboratory for critical reading and discussion of the manuscript. This work was supported in part by National Natural Science Foundation of China ( 81902487 ) and Scientific Research Training Program for Young Talents (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) to J.C., by National Natural Science Foundation of China ( 81572413 ) to K.T. and by US National Institutes of Health (NIH) grants to W.W. ( GM094777 and CA177910 ).
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/12
Y1 - 2019/12
N2 - Deubiquitylating enzymes (DUBs) are proteases that remove the ubiquitin moiety from ubiquitylated substrates to antagonize the modification mediated by E3 ubiquitin ligases. Currently, DUBs have been found to play critical roles in the regulation of various physiological or pathological processes, such as embryogenesis, immune homeostasis, tumorigenesis and neurodegenerative diseases. Accumulating evidences have suggested that different DUBs exert distinct function such as oncogenic, tumor-suppressive or context-dependent roles in tumorigenesis, mainly by affecting the protein stability, enzymatic activity or subcellular localization of its substrates. Importantly, multiple potent inhibitors targeting the enzymatic activity of oncogenic DUBs have been developed and show promising anti-cancer efficacy in preclinical models. Thus, exploring the unique role of DUB enzymes and their downstream effectors will provide novel insights into the molecular basis of cancer development. Here, we review and summarize recent progress on DUB functional annotation, as well as its biochemical regulation, to provide a better understanding for cancer therapies by targeting DUBs.
AB - Deubiquitylating enzymes (DUBs) are proteases that remove the ubiquitin moiety from ubiquitylated substrates to antagonize the modification mediated by E3 ubiquitin ligases. Currently, DUBs have been found to play critical roles in the regulation of various physiological or pathological processes, such as embryogenesis, immune homeostasis, tumorigenesis and neurodegenerative diseases. Accumulating evidences have suggested that different DUBs exert distinct function such as oncogenic, tumor-suppressive or context-dependent roles in tumorigenesis, mainly by affecting the protein stability, enzymatic activity or subcellular localization of its substrates. Importantly, multiple potent inhibitors targeting the enzymatic activity of oncogenic DUBs have been developed and show promising anti-cancer efficacy in preclinical models. Thus, exploring the unique role of DUB enzymes and their downstream effectors will provide novel insights into the molecular basis of cancer development. Here, we review and summarize recent progress on DUB functional annotation, as well as its biochemical regulation, to provide a better understanding for cancer therapies by targeting DUBs.
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U2 - 10.1016/j.bbcan.2019.188312
DO - 10.1016/j.bbcan.2019.188312
M3 - Review article
C2 - 31449841
AN - SCOPUS:85071869593
VL - 1872
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
SN - 0304-419X
IS - 2
M1 - 188312
ER -