The Akt-SREBP nexus: cell signaling meets lipid metabolism.
Phosphatidylinositol 3'-kinase (PI3K) and Akt are signaling kinases involved in cell survival and proliferation. Recent evidence suggests that PI3K/Akt activates the sterol-regulatory element-binding proteins (SREBPs), master transcriptional regulators of lipid metabolism. The precise molecular mechanisms are controversial and differ between SREBP isoforms; proposed mechanisms include increased trafficking and processing of SREBP, reduced degradation, and involvement of the downstream signaling hub, mammalian target of rapamycin complex 1 (mTORC1). In this report, we explore the various mechanistic links between Akt and SREBP. We consider this relationship in diseases where Akt and lipids play crucial roles, including diabetes, viral infections and cancer, suggesting that this Akt-SREBP link provides fresh insights into human health and disease.
Krycer
James R
JR
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
Sharpe
Laura J
LJ
Luu
Winnie
W
Brown
Andrew J
AJ
D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D009369:Neoplasms / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051779:Sterol Regulatory Element Binding Proteins / Q000502:physiology*; D014777:Virus Diseases / Q000503:physiopathology
D051779:Sterol Regulatory Element Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt