ArticleCell cycle (Georgetown, Tex.)2016
The phosphorylation-dependent regulation of nuclear SREBP1 during mitosis links lipid metabolism and cell growth.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- A comprehensive transcriptional reference for severity and progression in spinal cord injury reveals novel translational biomarker genes.Journal of translational medicine · 2025Pooled it
- Perilipin1 mediates milk fat synthesis in bovine mammary epithelial cells through SREBP1 phosphorylation.Animal biotechnology · 2025Article
- NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia.Cancer biology & therapy · 2025Article
- The Functional Interaction Between PRDM16 and the SREBP Pathway Controls Lipid Metabolism.International journal of molecular sciences · 2025Article
- Review
- A Promising Prognostic Signature Consisting of Fatty Acid Metabolism Genes based on Machine Learning Predicts Biochemical Recurrence and Aids ARSI Therapy in Prostate Cancer.Journal of Cancer · 2025Article
- CTBP1 links metabolic syndrome to polycystic ovary syndrome through interruption of aromatase and SREBP1.Communications biology · 2024Article
- The roles and mechanisms of SREBP1 in cancer development and drug response.Genes & diseases · 2024Review
- MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis.Cell death discovery · 2024Article
- Let-7a-5p Regulates Animal Lipid Accumulation by Targeting Srebf2 and Thbs1 Signaling.International journal of molecular sciences · 2024Article
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- Integrative Proteomics and Phosphoproteomics Analysis of the Rat Adenohypophysis after GnRH Treatment.International journal of molecular sciences · 2023Article
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
- Posttranslational control of lipogenesis in the tumor microenvironment.Journal of hematology & oncology · 2022Review
- Timosaponin A3 Inhibits Palmitate and Stearate through Suppression of SREBP-1 in Pancreatic Cancer.Pharmaceutics · 2022Article
- The effect of bile salt diet supplementation on genes related to fat metabolism in yellow-feathered broilers.Veterinary world · 2022Article
- The SREBP-dependent regulation of cyclin D1 coordinates cell proliferation and lipid synthesis.Frontiers in oncology · 2022Article
- Loss of the Fbw7 tumor suppressor rewires cholesterol metabolism in cancer cells leading to activation of the PI3K-AKT signalling axis.Frontiers in oncology · 2022Article
- Suppressive role of E3 ubiquitin ligase FBW7 in type I diabetes in non-obese diabetic mice through mediation of ubiquitination of EZH2.Cell death discovery · 2021Article
- Lipidomics reveals that sustained SREBP-1-dependent lipogenesis is a key mediator of gefitinib-acquired resistance in EGFR-mutant lung cancer.Cell death discovery · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SREBP transcription factors are major regulators of lipid metabolism. Disturbances in lipid metabolism are at the core of several health issues facing modern society, including cardiovascular disease, obesity and diabetes. In addition, the role of lipid metabolism in cancer cell growth is receiving increased attention. Transcriptionally active SREBP molecules are unstable and rapidly degraded in a phosphorylation-dependent manner by Fbw7, a ubiquitin ligase that targets several cell cycle regulatory proteins for degradation. We have previously demonstrated that active SREBP1 is stabilized during mitosis. We have now delineated the mechanisms involved in the stabilization of SREBP1 in mitotic cells. This process is initiated by the phosphorylation of a specific serine residue in nuclear SREBP1 by the mitotic kinase Cdk1. The phosphorylation of this residue creates a docking site for a separate mitotic kinase, Plk1. Plk1 interacts with nuclear SREBP1 in mitotic cells and phosphorylates a number of residues in the C-terminal domain of the protein, including a threonine residue in close proximity of the Fbw7 docking site in SREBP1. The phosphorylation of these residues by Plk1 blocks the interaction between SREBP1 and Fbw7 and attenuates the Fbw7-dependent degradation of nuclear SREBP1 during cell division. Inactivation of SREBP1 results in a mitotic defect, suggesting that SREBP1 could regulate cell division. We propose that the mitotic phosphorylation and stabilization of nuclear SREBP1 during cell division provides a link between lipid metabolism and cell proliferation. Thus, the current study provides additional support for the emerging hypothesis that SREBP-dependent lipid metabolism may be important for cell growth.
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