YAP regulates an SGK1/mTORC1/SREBP-dependent lipogenic program to support proliferation and tissue growth

S Vaidyanathan; TM Salmi; RM Sathiqu; MJ McConville; AG Cox; KK Brown

Journal article

YAP regulates an SGK1/mTORC1/SREBP-dependent lipogenic program to support proliferation and tissue growth

S Vaidyanathan, TM Salmi, RM Sathiqu, MJ McConville, AG Cox, KK Brown

Developmental Cell | CELL PRESS | Published : 2022

DOI: 10.1016/j.devcel.2022.02.004

Abstract

The coordinated regulation of growth control and metabolic pathways is required to meet the energetic and biosynthetic demands associated with proliferation. Emerging evidence suggests that the Hippo pathway effector Yes-associated protein 1 (YAP) reprograms cellular metabolism to meet the anabolic demands of growth, although the mechanisms involved are poorly understood. Here, we demonstrate that YAP co-opts the sterol regulatory element-binding protein (SREBP)-dependent lipogenic program to facilitate proliferation and tissue growth. Mechanistically, YAP stimulates de novo lipogenesis via mechanistic target of rapamcyin (mTOR) complex 1 (mTORC1) signaling and subsequent activation of SREBP..

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University of Melbourne Researchers

Malcolm McConville Author

Andrew Cox Author

Kristin Brown Author

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Grants

Awarded by Victorian Cancer Agency

Funding Acknowledgements

S.V. is supported by an Australian Government Research Training Program Scholarship and the Peter MacCallum Cancer Foundation (Lester Peters Award). T.M.S. is supported by a Yayasan Dayadiri Scholarship and a University of Melbourne Research Scholarship. M.J.M. is supported by an NHMRC Principal Research Fellowship (APP1154540). A.G.C. is supported by an NHMRC Project Grant (GNT1146558), an NHMRC Investigator Grant (GNT1176650), and an ARC Discovery Project Grant (DP200102693). K.K.B. is supported by an NHMRC Project Grant (GNT1146642), an NHMRC Ideas Grant (GNT2004212), a VCA Mid-Career Research Fellowship (MCRF17020), and a Susan G. Komen Career Catalyst Research Grant (CCR18548354). A.G.C. and K.K.B. are also jointly supported by the Peter MacCallum Cancer Foundation (Ted and Lila Seehusen Foundation). We acknowledge support from the Peter MacCallum Cancer Centre Foundation and the Australian Cancer Research Foundation. This research used National Collaborative Research Infrastructure Strategy (NCRIS)-enabled metabolomics Australia infrastructure at the University of Melbourne, funded through BioPlatforms Australia. We extend our thanks also to the Peter MacCallum Cancer Centre Core Facilities and their staff who provided support for this work; namely the Centre for Advanced Histology & Microscopy and the Molecular Genomics Core and Bioinformatics Core Facilities. We also thank the staff involved at the University of Melbourne Zebrafish Core Facility (DRUM). Finally, we thank members of the Cox Laboratory and Brown Laboratory (Peter MacCallum Cancer Centre) for helpful discussions.