The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer.

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer.
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Cullin 7 E3 泛素连接酶在癌症中的功能分析

DOI:
10.1038/s41389-020-00276-w
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发表时间:
2020-10-31
期刊:
影响因子:
6.2
通讯作者:
Long J
Long J
中科院分区:
医学1区
文献类型:
--
作者:
Shi L;Du D;Peng Y;Liu J;Long J

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Cullin(CUL)蛋白在发育和癌症中具有重要作用,但由于其独特的分子结构,对CUL 7的研究很少。CUL 7与ROC 1环指蛋白形成复合物,只有两种F-box蛋白Fbxw 8和Fbxw 11与CUL 7结合。有趣的是,CUL 7可以通过形成一种新的复合物与其底物相互作用,这种复合物独立于这两种F-box蛋白。CUL-环连接酶7(CRL 7)的生物学意义表明,CRL 7不仅可以执行蛋白水解功能,而且还可以发挥非蛋白水解作用。在现有研究的基于CRL 7的E3连接酶中,CUL 7以上下文依赖性方式发挥肿瘤促进和抑制作用。目前,CUL 7在癌症中的机制仍不清楚,并且没有研究涉及靶向CUL 7的潜在疗法。与各种CRL 7衔接子的作用一致,靶向CRL 7可能是预防和治疗癌症的有效策略。我们系统地描述了最近的主要进展,了解CUL 7 E3连接酶在癌症中的作用,并进一步总结其在临床治疗中的潜在用途。
Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these two F-box proteins. The biological implications of CUL-ring ligase 7 (CRL7) suggest that the CRL7 may not only perform a proteolytic function but may also play a non-proteolytic role. Among the existing studied CRL7-based E3 ligases, CUL7 exerts both tumor promotion and suppression in a context-dependent manner. Currently, the mechanism of CUL7 in cancer remains unclear, and no studies have addressed potential therapies targeting CUL7. Consistent with the roles of the various CRL7 adaptors exhibit, targeting CRL7 might be an effective strategy for cancer prevention and treatment. We systematically describe the recent major advances in understanding the role of the CUL7 E3 ligase in cancer and further summarize its potential use in clinical therapy.
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期刊: TUMOR BIOLOGY
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