Phosphorylation dependent proteostasis of sterol regulatory element binding proteins.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1864(8): 1145-1156, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31067497
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-3ß, protein kinase A and 5' adenosine monophosphate-activated protein kinase regulates the mechanisms of RIP and stability of SREBP-1c and de novo lipogenesis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a Elemento Regulador de Esterol
/
Proteostase
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article