ArticleProtein & cell2021
POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation.
Article in Protein & cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- FTO-Catalysed Demethylation of LUR1 mRNA Suppresses Macrophage Lipid Accumulation and Aortic Atherosclerosis.Journal of cellular and molecular medicine · 2026Article
- A graph-based learning approach to predict the effects of gene perturbations on molecular phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Targeting C12ORF49-Mediated Ferroptosis in Hepatocellular Carcinoma.JGH open : an open access journal of gastroenterology and hepatology · 2026Review
- SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.Current opinion in lipidology · 2025Review
- Lipin1-dependent transcriptional inactivation of SREBPs contributes to selinexor sensitivity in multiple myeloma.Acta pharmacologica Sinica · 2025Article
- Effects of Cholesterol Metabolism on Corneal Endothelial Dysfunction in Patients With Type 1 Diabetes.Investigative ophthalmology & visual science · 2025Article
- Structural basis for substrate selectivity by site-one protease revealed by studies with a small-molecule inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- C12ORF49 inhibits ferroptosis in hepatocellular carcinoma cells via reprogramming SREBP1/SCD1-mediated lipid metabolism.Cell death discovery · 2025Article
- Systematic interrogation of functional genes underlying cholesterol and lipid homeostasis.Genome biology · 2025Article
- SREBP2 as a central player in cancer progression: potential for targeted therapeutics.Frontiers in pharmacology · 2025Review
- SPRING licenses S1P-mediated cleavage of SREBP2 by displacing an inhibitory pro-domain.Nature communications · 2024Article
- Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.Journal of lipid research · 2024Article
- Fatty acid-binding proteins 3, 7, and 8 bind cholesterol and facilitate its egress from lysosomes.The Journal of cell biology · 2024Article
- SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P.Molecular and cellular biology · 2024Article
- Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene.Communications biology · 2023Article
- Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling.Nature communications · 2023Article
- Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites.Nature communications · 2023Article
- Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans.Nature communications · 2023Article
- Lysosomal cholesterol accumulation is commonly found in most peroxisomal disorders and reversed by 2-hydroxypropyl-β-cyclodextrin.Science China. Life sciences · 2023Article
- Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.
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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.