Progesterone Receptor Membrane Component 1 and 2 regulate granulosa cell mitosis and survival through a NF ΚB-dependent mechanism.

Progesterone Receptor Membrane Component 1 and 2 regulate granulosa cell mitosis and survival through a NFΚB-dependent mechanism. Biol Reprod. 2019 Mar 16;: Authors: Peluso JJ, Pru CA, Liu X, Kelp NC, Pru JK Abstract Progesterone Receptor Membrane Component 1 (PGRMC1) interacts with PGRMC2 and disrupting this interaction in spontaneously immortalized granulosa cells (SIGCS) leads to an inappropriate entry into the cell cycle, mitotic arrest and ultimately cell death. The present study revealed that PGRMC1 and PGRMC2 localize to the cytoplasm of murine granulosa cells of non-atretric follicles with their staining intensity being somewhat diminished in granulosa cells of atretic follicles. Compared to controls (Pgrmc1fl/fl), the rate at which granulosa cells entered the cell cycle increased in non-atretic and atretic follicles of mice in which Pgrmc1 was conditionally deleted (Pgrmc1d/d) from granulosa cells. This increased rate of entry into the cell cycle was associated with a ≥ 2 fold increase in follicular atresia and the nuclear localization of Nuclear Factor-Kappa-B Transcription Factor P65; (NFΚB/p65, or RELA). GTPase Activating Protein Binding Protein 2 (G3BP2) binds NFΚB/p65 through an interaction with NFΚB Inhibitor Alpha (IκBα), thereby maintaining NFΚB/p65's cytoplasmic localization and restricting its transcriptional activity. Since PGRMC1 and PGRMC2 bind G3BP2, studies were designed to assess the functional rel...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research