SIRT7 safeguards ERα proteostasis via deacetylation-dependent degradation of unliganded and misfolded receptors.

ABSTRACT: SIRT7 has been implicated in diverse physiological and pathological processes, yet its role in sexual dimorphism and the underlying molecular mechanisms remains insufficiently explored. Given that ERα-mediated estrogen signaling is a central regulator of sexual dimorphism and that ERα undergoes stringent quality control to preserve signaling sensitivity, we investigated whether SIRT7 and ERα are mechanistically connected. Here, we identify SIRT7 as a molecular inspector that safeguards the quality of estrogen receptor α (ERα) to fine-tune estrogen signaling through the regulation of ERα proteostasis. Under estrogen-deprived conditions or in the presence of misfolded ERα, SIRT7 deacetylates ERα and promotes its degradation through the E3 ubiquitin ligase STUB1, thereby maintaining a functio

SUBMITTER: Cao M 

PROVIDER: S-EPMC12919253 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature