The BRCA2 missense mutation K2497R suppressed self-degradation and increased ATP production and cell proliferation.
The BRCA2 missense mutation K2497R suppressed self-degradation and increased ATP production and cell proliferation.
复制标题
BRCA2 错义突变 K2497R 抑制自我降解并增加 ATP 产生和细胞增殖。
DOI：
10.1016/j.bbrc.2021.12.073
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Miki Y.
中科院分区：
文献类型：
--
作者：
Enkhbat G;Nakanishi A;Miki Y.
乳腺癌易感基因2（BRCA 2）介导细胞周期S期的基因组维持，在复制应激、中心体复制和胞质分裂中发挥重要作用。在这项研究中，我们发现，一个小的热休克蛋白，HSP 27，相互作用，并参与了雌激素处理的MCF-7细胞中BRCA 2的降解。据报道，BRCA 2降解需要C-末端区域的泛素化;因此，产生氨基酸（aa）残基2241-2940的片段，并测定其在放线菌酮（CHX）处理后的降解。结果表明，氨基酸2491-2580对BRCA 2的降解有影响，尤其是赖氨酸（Lys）2497。此外，与表达野生型BRCA 2-FLAG的细胞相比，K2497 A/R突变增加了DLD-1（BRCA 2敲除）细胞的ATP产生和增殖。值得注意的是，一个单一的残基，Lys 2497，影响BRCA 2降解，和K2497 R据报道是一个错义突变遗传性乳腺癌。
Breast cancer susceptibility gene 2 (BRCA2) mediates genome maintenance during the S phase of the cell cycle, with important roles in replication stress, centrosome replication, and cytokinesis. In this study, we showed that a small heat shock protein, HSP27, interacted with and participated in the degradation of BRCA2 in estrogen-treated MCF-7 cells. BRCA2 degradation reportedly requires ubiquitination of the C-terminal region; thus, fragments of amino acid (aa) residues 2241–2940 were produced and assayed for their degradation following cycloheximide (CHX) treatment. The results showed that aa 2491–2580 affected the degradation of BRCA2, especially lysine (Lys) 2497. Furthermore, the K2497 A/R mutation increased ATP production and the proliferation of DLD-1 (BRCA2 knockout) cells compared to the cells expressing wild-type BRCA2-FLAG. Notably, a single residue, Lys2497, affected BRCA2 degradation, and K2497R is reportedly a missense mutation in hereditary breast cancer.