TY - JOUR
T1 - Functional analysis of Cullin 3 E3 ligases in tumorigenesis
AU - Cheng, Ji
AU - Guo, Jianping
AU - Wang, Zhiwei
AU - North, Brian J.
AU - Tao, Kaixiong
AU - Dai, Xiangpeng
AU - Wei, Wenyi
N1 - Funding Information:
The authors sincerely apologize to all those colleagues whose important work was not cited in this paper owing to space limitations. They thank the members of Wei laboratory for critical reading and discussion of the manuscript. W.W. is a Leukemia & Lymphoma Society (LLS) research scholar. This work was supported in part by Scientific Research Training Program for Young Talents (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology ( 201701 )) to J.C., by National Natural Science Foundation of China ( 81572413 ) to K.T. and by US National Institutes of Health (NIH) grants to B.J.N. ( AG052627 ) and W.W. ( GM094777 and CA177910 ).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/1
Y1 - 2018/1
N2 - Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner. Among the extensively studied CRL3-based E3 ligases, the role of the adaptor protein SPOP (speckle type BTB/POZ protein) in tumorigenesis appears to be tissue or cellular context dependent. Specifically, SPOP acts as a tumor suppressor via destabilizing downstream oncoproteins in many malignancies, especially in prostate cancer. However, SPOP has largely an oncogenic role in kidney cancer. Keap1, another well-characterized CRL3 adaptor protein, likely serves as a tumor suppressor within diverse malignancies, mainly due to its specific turnover of its downstream oncogenic substrate, NRF2 (nuclear factor erythroid 2-related factor 2). In accordance with the physiological role the various CRL3 adaptors exhibit, several pharmacological agents have been developed to disrupt its E3 ligase activity, therefore blocking its potential oncogenic activity to mitigate tumorigenesis.
AB - Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner. Among the extensively studied CRL3-based E3 ligases, the role of the adaptor protein SPOP (speckle type BTB/POZ protein) in tumorigenesis appears to be tissue or cellular context dependent. Specifically, SPOP acts as a tumor suppressor via destabilizing downstream oncoproteins in many malignancies, especially in prostate cancer. However, SPOP has largely an oncogenic role in kidney cancer. Keap1, another well-characterized CRL3 adaptor protein, likely serves as a tumor suppressor within diverse malignancies, mainly due to its specific turnover of its downstream oncogenic substrate, NRF2 (nuclear factor erythroid 2-related factor 2). In accordance with the physiological role the various CRL3 adaptors exhibit, several pharmacological agents have been developed to disrupt its E3 ligase activity, therefore blocking its potential oncogenic activity to mitigate tumorigenesis.
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U2 - 10.1016/j.bbcan.2017.11.001
DO - 10.1016/j.bbcan.2017.11.001
M3 - Review article
C2 - 29128526
AN - SCOPUS:85034055870
VL - 1869
SP - 11
EP - 28
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
SN - 0304-419X
IS - 1
ER -