关于 SCFFBXW7 E3 泛素连接酶抑制肿瘤作用的分子见解和临床意义。

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-06-21 DOI:10.1016/j.bbcan.2024.189140
Yihang Qi , Abdol-Hossein Rezaeian , Jingchao Wang , Daoyuan Huang , Hong Chen , Hiroyuki Inuzuka , Wenyi Wei
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引用次数: 0

摘要

FBXW7 是特征最明显的 F-box 蛋白之一,是 SKP1-CUL1-F-box (SCF)E3 连接酶复合物的底物受体亚基。SCFFBXW7 负责降解多种致癌蛋白,如细胞周期蛋白 E、c-MYC、c-JUN、NOTCH 和 MCL1。因此,FBXW7 在很大程度上是一种主要的肿瘤抑制因子。根据这一观点,FBXW7 基因突变或下调已在子宫内膜癌、结直肠癌、肺癌和乳腺癌等多种恶性肿瘤中被发现和报道,这些突变或下调促进了癌细胞的增殖、侵袭、迁移和耐药性。因此,回顾新发现的 FBXW7 在生理和病理条件下的调控和抑瘤功能,对于制定治疗 FBXW7 改变的癌症的有效策略至关重要。鉴于越来越多的证据揭示了FBXW7的抑瘤活性和作用,我们在此更新了FBXW7的上下游信号转导,包括FBXW7泛素底物、FBXW7的多级调控机制、FBXW7在癌症中的失调,并探讨了针对FBXW7调控因子和下游效应因子的有前景的癌症疗法,以提供一个全面的FBXW7图谱,促进该领域的研究。
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Molecular insights and clinical implications for the tumor suppressor role of SCFFBXW7 E3 ubiquitin ligase

FBXW7 is one of the most well-characterized F-box proteins, serving as substrate receptor subunit of SKP1-CUL1-F-box (SCF) E3 ligase complexes. SCFFBXW7 is responsible for the degradation of various oncogenic proteins such as cyclin E, c-MYC, c-JUN, NOTCH, and MCL1. Therefore, FBXW7 functions largely as a major tumor suppressor. In keeping with this notion, FBXW7 gene mutations or downregulations have been found and reported in many types of malignant tumors, such as endometrial, colorectal, lung, and breast cancers, which facilitate the proliferation, invasion, migration, and drug resistance of cancer cells. Therefore, it is critical to review newly identified FBXW7 regulation and tumor suppressor function under physiological and pathological conditions to develop effective strategies for the treatment of FBXW7-altered cancers. Since a growing body of evidence has revealed the tumor-suppressive activity and role of FBXW7, here, we updated FBXW7 upstream and downstream signaling including FBXW7 ubiquitin substrates, the multi-level FBXW7 regulatory mechanisms, and dysregulation of FBXW7 in cancer, and discussed promising cancer therapies targeting FBXW7 regulators and downstream effectors, to provide a comprehensive picture of FBXW7 and facilitate the study in this field.

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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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