ArticleBioscience reports2015
Glycogen synthase kinase-3-mediated phosphorylation of serine 73 targets sterol response element binding protein-1c (SREBP-1c) for proteasomal degradation.
Article in Bioscience reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Circular RNAs in Liver Diseases.Advances in experimental medicine and biology · 2025Review
- Article
- Mitochondrial translation failure represses cholesterol gene expression via Pyk2-Gsk3β-Srebp2 axis.Life science alliance · 2024Article
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Dietary High Levels of Coconut Oil Replacing Fish Oil Did Not Affect Growth, but Promoted Liver Lipid Deposition of Orange-Spotted Groupers (Animals : an open access journal from MDPI · 2024Article
- Regulation of PI3K signaling in cancer metabolism and PI3K-targeting therapy.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
- The m6A modification-mediated OGDHL exerts a tumor suppressor role in ccRCC by downregulating FASN to inhibit lipid synthesis and ERK signaling.Cell death & disease · 2023Article
- Cdk8 attenuates lipogenesis by inhibiting SREBP-dependent transcription in Drosophila.Disease models & mechanisms · 2022Article
- The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous.Biological research · 2021Review
- Review
- Insulin-induced de novo lipid synthesis occurs mainly via mTOR-dependent regulation of proteostasis of SREBP-1c.Molecular and cellular biochemistry · 2020Article
- Down-Regulation of SREBP via PI3K/AKT/mTOR Pathway Inhibits the Proliferation and Invasion of Non-Small-Cell Lung Cancer Cells.OncoTargets and therapy · 2020Article
- Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats.Biology of sex differences · 2018Article
- Physiological functions of FBW7 in cancer and metabolism.Cellular signalling · 2018Review
- p53 and metabolism: from mechanism to therapeutics.Oncotarget · 2018Review
- Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition.Frontiers in immunology · 2018Article
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- GSK-3-mediated phosphorylation couples ER-Golgi transport and nuclear stabilization of the CREB-H transcription factor to mediate apolipoprotein secretion.Molecular biology of the cell · 2017Article
- Glycogen Synthase Kinase 3 (GSK-3)-mediated Phosphorylation of Uracil N-Glycosylase 2 (UNG2) Facilitates the Repair of Floxuridine-induced DNA Lesions and Promotes Cell Survival.The Journal of biological chemistry · 2016Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Sterol regulatory element binding protein-1c (SREBP-1c) is a key transcription factor that regulates genes involved in the de novo lipid synthesis and glycolysis pathways. The structure, turnover and transactivation potential of SREBP-1c are regulated by macronutrients and hormones via a cascade of signalling kinases. Using MS, we have identified serine 73 as a novel glycogen synthase kinase-3 (GSK-3) phosphorylation site in the rat SREBP-1c purified from McA-RH7777 hepatoma cells. Our site-specific mutagenesis strategy revealed that the turnover of SREBP-1c, containing wild type, phospho-null (serine to alanine) or phospho-mimetic (serine to aspartic acid) substitutions, was differentially regulated. We show that the S73D mutant of pSREBP-1c, that mimicked a state of constitutive phosphorylation, dissociated from the SREBP-1c-SCAP complex more readily and underwent GSK-3-dependent proteasomal degradation via SCF(Fbw7) ubiquitin ligase pathway. Pharmacologic inhibition of GSK-3 or knockdown of GSK-3 by siRNA prevented accelerated degradation of SREBP-1c. As demonstrated by MS, SREBP-1c was phosphorylated in vitro by GSK-3β at serine 73. Phosphorylation of serine 73 also occurs in the intact liver. We propose that GSK-3-mediated phosphorylation of serine 73 in the rat SREBP-1c and its concomitant destabilization represents a novel mechanism involved in the inhibition of de novo lipid synthesis in the liver.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.