VGLL4 and MENIN function as TEAD1 corepressors to block pancreatic β cell proliferation.

Autor:	Li F; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: fenglimed@gmail.com., Liu R; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Negi V; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Yang P; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Lee J; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Jagannathan R; Division of Cardiology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA., Moulik M; Division of Cardiology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA., Yechoor VK; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: yechoorv@pitt.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jan 31; Vol. 42 (1), pp. 111904. Date of Electronic Publication: 2023 Jan 19.
DOI:	10.1016/j.celrep.2022.111904
Abstrakt:	TEAD1 and the mammalian Hippo pathway regulate cellular proliferation and function, though their regulatory function in β cells remains poorly characterized. In this study, we demonstrate that while β cell-specific TEAD1 deletion results in a cell-autonomous increase of β cell proliferation, β 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 β 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 β cell proliferation. In conclusion, we demonstrate that TEAD1 plays a critical role in β cell proliferation and identify VGLL4 and MENIN as TEAD1 corepressors in β cells. We propose that these could be targeted to augment proliferation in β cells for reversing diabetes. Competing Interests: Declaration of interests No conflicts of interest, financial or otherwise, are declared by the authors. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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