Lactylation of CREB is required for FSH-induced proliferation and differentiation of ovarian granulosa cells.

ABSTRACT: Follicle-stimulating hormone (FSH) promotes follicular development by inducing the proliferation and differentiation of granulosa cells (GCs). This process is primarily attributed to the activation of the canonical G protein-coupled receptor (GPCR)/adenylyl cyclase/cAMP/PKA/CREB signaling pathway. Here, we revealed a novel mechanism wherein FSH promotes GCs proliferation and differentiation by stimulating cAMP response element-binding protein (CREB) lactylation. Specifically, FSH induced CREB lactylation at lysine 136 (K136la), leading to CREB phosphorylation at serine 133, which facilitated CREB/CBP/P300 complex formation for transcription activation. Moreover, K136la alone directly recruited CBP/P300, triggering transcriptional surges of proliferation and differentiation genes by binding

SUBMITTER: Wu G 

PROVIDER: S-EPMC12448862 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature