| First Author | Peluso JJ | Year | 2019 |
| Journal | Biol Reprod | Volume | 100 |
| Issue | 6 | Pages | 1571-1580 |
| PubMed ID | 30877763 | Mgi Jnum | J:277227 |
| Mgi Id | MGI:6316750 | Doi | 10.1093/biolre/ioz043 |
| Citation | Peluso JJ, et al. (2019) Progesterone receptor membrane component 1 and 2 regulate granulosa cell mitosis and survival through a NFKappaB-dependent mechanism. Biol Reprod 100(6):1571-1580 |
| abstractText | 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 nonatretric 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 nonatretic 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; (NFKappaB/p65, or RELA). GTPase activating protein binding protein 2 (G3BP2) binds NFKappaB/p65 through an interaction with NFKappaB inhibitor alpha (IkappaBalpha), thereby maintaining NFKappaB/p65''s cytoplasmic localization and restricting its transcriptional activity. Since PGRMC1 and PGRMC2 bind G3BP2, studies were designed to assess the functional relationship between PGRMC1, PGRMC2, and NFKappaB/p65 in SIGCs. In these studies, disrupting the interaction between PGRMC1 and PGRMC2 increased the nuclear localization of NFKappaB/p65, and depleting PGRMC1, PGRMC2, or G3BP2 increased NFKappaB transcriptional activity and the progression into the cell cycle. Taken together, these studies suggest that PGRMC1 and 2 regulate granulosa cell cycle entry in follicles by precisely controlling the localization and thereby the transcriptional activity of NFKappaB/p65. |
