α-连心蛋白在组织完整性、修复和胚胎发育方面起着关键作用。然而，α-连心蛋白的翻译后修饰以及在调节癌症进展方面的相关作用仍不清楚。在这里，我们报告了α-连心蛋白被p300乙酰化，并确定了三个乙酰化位点，K45、K866和K881。与此相反，α-连心蛋白的乙酰化可以被去乙酰化酶HDAC6逆转。机理上，α-连心蛋白的乙酰化通过阻断α-连心蛋白和Yap1之间的相互作用来释放转录共激活因子Yes-associated protein 1（Yap1），并促进Yap1在细胞核中的积累。通过这种机制，乙酰化削弱了α-连心蛋白抑制乳腺癌细胞增殖和小鼠肿瘤生长的能力。同时，我们显示CDDP诱导α-连心蛋白的乙酰化，并且乙酰化的α-连心蛋白在CDDP条件下抵抗细胞凋亡。此外，乙酰化抑制了α-连心蛋白的蛋白酶体依赖性降解，从而增强了α-连心蛋白的稳定性以进行储存。综上所述，我们的结果表明，α-连心蛋白可被乙酰化，这是Yap1亚细胞分布和乳腺癌发生的重要事件。© 2023. 作者, 授予Springer Nature America, Inc.独家许可。

α-Catenin plays a critical role in tissue integrity, repair, and embryonic development. However, the post-translational modifications of α-catenin and the correlative roles in regulating cancer progression remain unclear. Here, we report that α-catenin is acetylated by p300, and identify three acetylation sites, K45, K866, and K881. Conversely, α-catenin acetylation can be reversed by deacetylase HDAC6. Mechanistically, α-catenin acetylation releases the transcriptional coactivator Yes-associated protein 1 (Yap1) by blocking the interaction between α-catenin and Yap1, and promotes the accumulation of Yap1 in the nucleus. Through this mechanism, acetylation weakens the capacity of α-catenin to inhibit breast cancer cell proliferation and tumor growth in mice. Meanwhile, we show that CDDP induces acetylation of α-catenin, and acetylated α-catenin resists the apoptosis under CDDP conditions. Additionally, acetylation inhibits the proteasome-dependent degradation of α-catenin, thus enhancing the stability of α-catenin for storage. Taken together, our results demonstrate that α-catenin can be acetylated, an event that is key for the subcellular distribution of Yap1 and subsequent facilitation of breast tumorigenesis.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.