Lee Ok-Hee, Lee Jinkyoung, Lee Keun Ho, Woo Yun Mi, Kang Ju-Hee, Yoon Ho-Geun, Bae Soo-Kyung, Songyang Zhou, Oh Seung Hyun, Choi Youngsok
Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Republic of Korea.
Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Republic of Korea.
Biochim Biophys Acta. 2015 Feb;1853(2):409-21. doi: 10.1016/j.bbamcr.2014.11.007. Epub 2014 Nov 15.
The tripartite motif containing (TRIM) proteins are a large family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways. Here, we show that TRIM15 co-localized to focal adhesions through homo-dimerization and significantly suppressed cell migration. Domain mapping analysis indicated that B-box2 and PRY domains were essential for TRIM15 localization to focal adhesions and inhibition of cell migration. Our protein-protein interaction screen of TRIM15 with the integrin adhesome identified several TRIM15 interacting proteins including coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. TRIM15 expression was tissue-restricted and downregulated in colon cancer. Level of TRIM15 expression was associated with colon cancer cell migration, as well as both in vitro and in vivo tumor growth. These data provide novel insights into the role of TRIM15 as an additional component of the integrin adhesome, regulating cell migration, and suggest that TRIM15 may function as a tumor suppressor of colon cancer.
含三联基序（TRIM）蛋白是一个大家族的蛋白质，它们参与了许多生物学过程，包括细胞分化、凋亡、转录调控和信号通路。在此，我们表明TRIM15通过同二聚化定位于粘着斑，并显著抑制细胞迁移。结构域定位分析表明，B-box2和PRY结构域对于TRIM15定位于粘着斑和抑制细胞迁移至关重要。我们对TRIM15与整合素粘附体进行的蛋白质-蛋白质相互作用筛选，鉴定出几种与TRIM15相互作用的蛋白质，包括冠蛋白1B、皮层肌动蛋白、细丝蛋白结合LIM蛋白1和血管舒张刺激磷蛋白，它们都参与肌动蛋白细胞骨架动力学。TRIM15的表达具有组织限制性，在结肠癌中下调。TRIM15的表达水平与结肠癌细胞迁移以及体外和体内肿瘤生长均相关。这些数据为TRIM15作为整合素粘附体的一个额外组分在调节细胞迁移中的作用提供了新的见解，并表明TRIM15可能作为结肠癌的一种肿瘤抑制因子发挥作用。
