最近国际著名杂志BBA reviews on Cancer (影响因子9.3分)在线发表了哈佛大学医学院魏文毅教授的Cullin3 E3 酶的综述文章。苏州大学医学部王志伟教授是该文的作者之一。

Cullin 3酶(CRL3)在调节各种生理和病理过程,包括肿瘤事件中扮演关键角色。CRL3的底物通常包含一个 BTB 结构域, 它介导 Cullin3 和底物之间的相互作用,以促进它们的泛素化和随后的降解。CRL3的生物学意义已经被很好的描述,他们被发现扮演一个重要的角色,要么是癌基因,要么是抑癌基因，要么在不同的组织发挥不同的作用。在广泛研究的CRL3 E3酶中，SPOP发挥的作用也是依赖组织或细胞的类型。具体地说,SPOP在许多恶性肿瘤,特别是前列腺癌中,通过破坏下游癌基因的稳定性而起到肿瘤抑制作用。然而,SPOP在肾脏癌中的作用主要是致癌作用。Keap1,另一个研究比较多的CRL3 E3蛋白,可能主要在不同的恶性肿瘤中发挥肿瘤抑制作用,主要通过降解其下游致癌底物,NRF2。根据各种 CRL3 E3的生理作用,已经开发了一些试剂来扰乱其E3连接活性,从而阻断其潜在的致癌活性,以减轻肿瘤的发生。

苏州大学医学部王志伟教授说在这篇1万9千多字的综述里面，有8个表格，5个卡通图，作者们详细介绍了多个CRLE3酶的作用，功能和分子机制。这篇综述是读者全面了解CRLE3最新进展的一篇难得好文章。最后魏教授对CRLE3的科研发展进行了展望。这篇综述也是王志伟博士苏州大学教授和导师魏文毅教授的又一次合作的成果。

英文摘要

Biochim Biophys Acta. 2017 Nov 8. pii:S0304-419X(17)30179-8. doi: 10.1016/j.bbcan.2017.11.001. [Epub ahead of print]

Functional analysis of Cullin 3 E3 ligases in tumorigenesis.

Cheng J¹, Guo J², Wang Z³, North BJ², Tao K⁴, Dai X⁵, Wei W⁶.

Abstract

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 typeBTB/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 factor2). In accordance with the physiological role the various CRL3 adaptors exhibit, several pharmacological agents have been developed to disrupt its E3ligase activity, therefore blocking its potential oncogenic activity tomitigate tumorigenesis.