SREBP Activity Is Regulated by mTORC1 and Contributes to Akt-Dependent Cell Growth

By T. Porstmann, Claudio R. Santos, B. Griffiths, Megan Cully, Mary Y. Wu, S. Leevers, J. Griffiths, Yuen-Li Chung, A. Schulze. Cell Metabolism, 2008

1,376 citations recorded by the source corpus.

Summary Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis of macromolecules. The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1). Here we show that Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear accumulation of the mature form of the sterol responsive element binding protein (SREBP1) and expression of SREBP target genes was blocked by the mTORC1 inhibitor rapamycin. We also show that silencing of SREBP blocks Akt-dependent lipogenesis and attenuates the increase in cell size in response to Akt activation in vitro. Silencing of dSREBP in flies caused a reduction in cell and organ size and blocked the induction of cell growth by dPI3K. Our results suggest that the PI3K/Akt/TOR pathway regulates protein and lipid biosynthesis in an orchestrated manner and that both processes are required for cell growth.

Subfields: Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/5cc767f1c97f54237f8edcd202ce06fdca6838ba

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Surgery

Citations in the corpus

Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP‐1c (2010, background): “[62] have shown in retinal epithelial cells that mTORC1 activity is necessary for PKB/Akt-induced SREBP1c maturation and transcription and lipogenesis.”
Metabolic Regulation of T Lymphocytes (2013, background): “SREBP2 is also activated by mTORC1 to promote lipid synthesis (66).”
An emerging role of mTOR in lipid biosynthesis (2009, neutral): “As discussed in the previous section, mTORC1 promotes lipid synthesis by increasing SREBP-1 cleavage and activation [10].”
Metabolic control of YAP and TAZ by the mevalonate pathway (2014, background): “Indeed, nSREBP transgenic mice develop a strongly enlarged fatty liver while SREBP knock-out in drosophila caused reduction in organ size (Brown and Goldstein, 1997; Horton et al., 2003; Knebel et al., 2012; Porstmann et al., 2008) (Fig.”
Reprogramming of fatty acid metabolism in cancer (2019, background): “Several metabolic processes are activated by mTORC1, including oxidative phosphorylation by promoting mitochondrial biosynthesis,(91) sustaining de novo nucleotide synthesis(92) and lipogenesis.(93) The processing of the lipogenesis transcriptional regulator SREBP1 into its mature active form is str”
Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis (2020, background): “To investigate if mTORC1 regulates ferroptosis through modulating cellular lipid metabolism, we examined a central regulator of lipid synthesis, SREBP1 (20, 21), which was recently demonstrated as a downstream target of mTORC1 activity (22, 25, 34, 35).”
The LKB1-AMPK pathway: metabolism and growth control in tumor suppression (2009, background): “mTORC1 signalling is required for nuclear accumulation of SREBP1 and the induction of SREBP1 target gene”
mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. (2013, background): “…energy metabolism by stimulating the activity of several transcriptional regulators such as PPARg coactivator-1a (PGC-1a), sterol Inc. regulatory element-binding protein 1/2 (SREBP1/2), and hypoxia inducible factor-1a (HIF-1a) (Cunningham et al., 2007; Düvel et al., 2010; Porstmann et al., 2008).”
Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress (2010, background): “Akt, along with other kinases downstream of growth factor signaling, such as MAPK and p90 RSK1, phosphorylates TSC2 (Ballif et al., 2005; Li et al., 2003; Potter et al., 2002; Roux et al., 2004; Tee et al., 2003a).”
The interaction of hepatic lipid and glucose metabolism in liver diseases. (2012, background): “960 Journal of Hepatology 201 stress and inhibits autophagy, a novel pathway in the biology of hepatic lipid droplets [79,80].”