YAP regulates an SGK1/mTORC1/SREBP-dependent lipogenic program to support proliferation and tissue growth
Date
2022
Authors
Vaidyanathan, S.
Salmi, T.M.
Sathiqu, R.M.
McConville, M.J.
Cox, A.G.
Brown, K.K.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Developmental Cell, 2022; 57(6):719-731.e8
Statement of Responsibility
Srimayee Vaidyanathan, Talhah M. Salmi, Rasan M. Sathiqu, MalcolmJ.McConville, AndrewG.Cox, Kristin K. Brown
Conference Name
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. Importantly, YAP-dependent regulation of serum- and glucocorticoid-regulated kinase 1 (SGK1) is required to activate mTORC1/SREBP and stimulate de novo lipogenesis. We also find that the SREBP target genes fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) are conditionally required to support YAP-dependent proliferation and tissue growth. These studies reveal that de novo lipogenesis is a metabolic vulnerability that can be targeted to disrupt YAP-dependent proliferation and tissue growth.
School/Discipline
Dissertation Note
Provenance
Description
additional pages e1-e8
Access Status
Rights
© 2022 Elsevier Inc