Phosphorylation dependent proteostasis of sterol regulatory element binding proteins

Research output: Contribution to journalReview article

Abstract

Lipid homeostasis is critically dependent on the liver. Hepatic genes involved in lipid biosynthesis are controlled by combinatorial actions of multiple transcription factors that include three sterol regulatory element binding proteins (SREBPs), carbohydrate responsive element binding protein, liver X receptors, and others. SREBP-1c, a seminal regulator of de novo lipogenesis, resides in the endoplasmic reticulum as a transcriptionally inert precursor and must undergo a regulated intramembrane proteolysis (RIP)prior to its nuclear translocation as a bone fide transcription factor. The regulation of biosynthesis, turnover and actions of SREBP-1c and lipogenesis are mechanistically linked to signaling kinases, canonically induced by macronutrients and insulin. Here, we briefly review the evidence showing that phosphorylation of SREBP-1c and its interacting partners, catalyzed by phosphatidyl inositol-3-kinase, protein kinase B, mechanistic target of rapamycin complex 1 and 2, mitogen activated protein kinases, glycogen synthase kinase-3β, protein kinase A and 5′ adenosine monophosphate-activated protein kinase regulates the mechanisms of RIP and stability of SREBP-1c and de novo lipogenesis.

Original languageEnglish (US)
Pages (from-to)1145-1156
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1864
Issue number8
DOIs
StatePublished - Aug 1 2019

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Sterol Regulatory Element Binding Proteins
Sterol Regulatory Element Binding Protein 1
Lipogenesis
Phosphorylation
Proteolysis
Transcription Factors
Phosphotransferases
Glycogen Synthase Kinase 3
Lipids
Proto-Oncogene Proteins c-akt
Liver
Adenosine Monophosphate
Phosphatidylinositols
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
Endoplasmic Reticulum
Protein Kinases
Carrier Proteins
Homeostasis
Carbohydrates

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Phosphorylation dependent proteostasis of sterol regulatory element binding proteins. / Raghow, Rajendra; Dong, Qingming; Elam, Marshall.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1864, No. 8, 01.08.2019, p. 1145-1156.

Research output: Contribution to journalReview article

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