Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Cells. 2022 Aug 8;11(15):2464. doi: 10.3390/cells11152464.
Increasing attention has been paid to the biological roles of tripartite motif-containing (TRIM) family proteins, which typically function as E3 ubiquitin ligases. Estrogen-responsive finger protein (Efp), a member of the TRIM family proteins, also known as TRIM25, was originally identified as a protein induced by estrogen and plays critical roles in promoting endocrine-related cancers, including breast cancer, endometrial cancer, and prostate cancer. The pathophysiological importance of Efp made us interested in the roles of other TRIM family proteins that share a similar structure with Efp. Based on a phylogenetic analysis of the C-terminal region of TRIM family proteins, we focused on TRIM47 as a protein belonging to the same branch as Efp. TRIM47 is a poor prognostic factor in both breast cancer and prostate cancer. Atypical lysine-27-like poly-ubiquitination was involved in the underlying mechanism causing endocrine resistance in breast cancer. We also discuss the functions of Efp and TRIM47 in other types of cancers and innate immunity by introducing substrates the are modified by poly-ubiquitination.
越来越多的人开始关注三基序蛋白（TRIM）家族蛋白的生物学作用，这些蛋白通常作为 E3 泛素连接酶发挥作用。雌激素反应指蛋白（Efp）是 TRIM 家族蛋白的一个成员，也称为 TRIM25，最初被鉴定为一种由雌激素诱导的蛋白，在促进包括乳腺癌、子宫内膜癌和前列腺癌在内的内分泌相关癌症中发挥着关键作用。Efp 的病理生理学重要性引起了我们对其他具有与 Efp 相似结构的 TRIM 家族蛋白的作用的兴趣。基于对 TRIM 家族蛋白 C 末端区域的系统发育分析，我们将重点放在 TRIM47 上，它是与 Efp 属于同一分支的蛋白。TRIM47 是乳腺癌和前列腺癌的不良预后因素。非典型赖氨酸-27 样多泛素化参与了导致乳腺癌内分泌耐药的潜在机制。我们还通过介绍被多泛素化修饰的底物，讨论了 Efp 和 TRIM47 在其他类型癌症和天然免疫中的功能。
