Acetylation-dependent regulation of TPD52 isoform 1 modulates chaperone-mediated autophagy in prostate cancer
Acetylation-dependent regulation of TPD52 isoform 1 modulates chaperone-mediated autophagy in prostate cancer
复制标题
TPD52亚型1的乙酰化依赖性调节调节前列腺癌中伴侣介导的自噬
DOI：
10.1080/15548627.2021.1917130
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发表时间：
2021-05-27
期刊：
影响因子：
13.3
通讯作者：
Li, Lei
中科院分区：
文献类型：
--
作者：
Fan, Yizeng;Hou, Tao;Li, Lei
Aberrant chaperone-mediated autophagy (CMA) activation has been suggested as a tumorigenesis-promoting event in various cancers, although its roles in prostate cancer (PCa) remain elusive. Emerging evidence indicates that TPD52 isoform 1, a prostate-specific and androgen-responsive gene, contributes to the malignant progression of PCa. Here, we demonstrate that TPD52 enhances CMA activation by interacting with HSPA8/HSC70 and enhancing substrate degradation in PCa. Elevation of TPD52 is essential for CMA-induced PCa cell proliferation and stress resistance in vitro and in vivo. Furthermore, TPD52 is acetylated by KAT2B at K163, which is a process that can be antagonized by HDAC2. Inactivation of HDAC2 results in elevated TPD52 acetylation, which compromises the interaction between TPD52 and HSPA8, leading to impaired CMA function and tumor growth in vivo. Taken together, our findings reveal that acetylation-dependent regulation of TPD52 modulates CMA oncogenic function in PCa, thereby suggesting the possibility of targeting the TPD52-mediated CMA pathway to control the progression of PCa.
