| First Author | Li F | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 1 | Pages | 111904 |
| PubMed ID | 36662616 | Mgi Jnum | J:333436 |
| Mgi Id | MGI:7432242 | Doi | 10.1016/j.celrep.2022.111904 |
| Citation | Li F, et al. (2023) VGLL4 and MENIN function as TEAD1 corepressors to block pancreatic beta cell proliferation. Cell Rep 42(1):111904 |
| abstractText | TEAD1 and the mammalian Hippo pathway regulate cellular proliferation and function, though their regulatory function in beta cells remains poorly characterized. In this study, we demonstrate that while beta cell-specific TEAD1 deletion results in a cell-autonomous increase of beta cell proliferation, beta cell-specific deletion of its canonical coactivators, YAP and TAZ, does not affect proliferation, suggesting the involvement of other cofactors. Using an improved split-GFP system and yeast two-hybrid platform, we identify VGLL4 and MENIN as TEAD1 corepressors in beta cells. We show that VGLL4 and MENIN bind to TEAD1 and repress the expression of target genes, including FZD7 and CCN2, which leads to an inhibition of beta cell proliferation. In conclusion, we demonstrate that TEAD1 plays a critical role in beta cell proliferation and identify VGLL4 and MENIN as TEAD1 corepressors in beta cells. We propose that these could be targeted to augment proliferation in beta cells for reversing diabetes. |
