ArticleProtein & cell2013
Upregulation of SIRT1 by 17β-estradiol depends on ubiquitin-proteasome degradation of PPAR-γ mediated by NEDD4-1.
Article in Protein & cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- TRIM28 orchestrates SUMO-ubiquitin crosstalk to stabilize PPARG and drive bladder cancer progression.Cell death & disease · 2026Article
- Article
- Lathyrol Exerts Anti-Pulmonary Fibrosis Effects by Activating PPARγ to Inhibit the TGF-β/Smad Pathway.International journal of molecular sciences · 2025Article
- The deubiquitinase USP28 maintains the expression of PPARγ and its inactivation protects mice from diet-induced MASH and hepatocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- Targeting PPARγ via SIAH1/2-mediated ubiquitin-proteasomal degradation as a new therapeutic approach in luminal-type bladder cancer.Cell death & disease · 2024Article
- Microglial Pdcd4 deficiency mitigates neuroinflammation-associated depression via facilitating Daxx mediated PPARγ/IL-10 signaling.Journal of neuroinflammation · 2024Article
- Intranasal Delivery of Mitochondria Attenuates Brain Injury by AMPK and SIRT1/PGC-1α Pathways in a Murine Model of Photothrombotic Stroke.Molecular neurobiology · 2024Article
- Article
- Decoding the secrets of longevity: unraveling nutraceutical and miRNA-Mediated aging pathways and therapeutic strategies.Frontiers in aging · 2024Review
- Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics.Endocrine reviews · 2023Review
- Estradiol as the Trigger of Sirtuin-1-Dependent Cell Signaling with a Potential Utility in Anti-Aging Therapies.International journal of molecular sciences · 2023Review
- Eldecalcitol prevented OVX-induced osteoporosis through inhibiting BMSCs senescence by regulating the SIRT1-Nrf2 signal.Frontiers in pharmacology · 2023Article
- Gut Microbiota and Sex Hormones: Crosstalking Players in Cardiometabolic and Cardiovascular Disease.International journal of molecular sciences · 2022Review
- Up-regulation of SIRT1 induced by 17beta-estradiol promotes autophagy and inhibits apoptosis in osteoblasts.Aging · 2021Article
- Review
- Bioinformatic gene analysis for potential therapeutic targets of Huntington's disease in pre-symptomatic and symptomatic stage.Journal of translational medicine · 2020Article
- Aryl hydrocarbon receptor (AhR) regulates adipocyte differentiation by assembling CRL4B ubiquitin ligase to target PPARγ for proteasomal degradation.The Journal of biological chemistry · 2019Article
- Article
- Sex, gut microbiome, and cardiovascular disease risk.Biology of sex differences · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
17β-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and a down-regulation of PPARγ. The decrease in PPARγ expression is mediated by increased degradation of PPARγ. Here we report that PPARγ is ubiquitinated by HECT E3 ubiquitin ligase NEDD4-1 and degraded, along with PPARγ, in response to E2 stimulation. The PPARγ interacts with ubiquitin ligase NEDD4-1 through a conserved PPXY-WW binding motif. The WW3 domain in NEDD4-1 is critical for binding to PPARΓ. NEDD4-1 overexpression leads to PPARγ ubiquitination and reduced expression of PPARγ. Conversely, knockdown of NEDD4-1 by specific siRNAs abolishes PPARΓ ubiquitination. These data indicate that NEDD4-1 is the E3 ubiquitin ligase responsible for PPARγ ubiquitination. Here, we show that NEDD4-1 delays cellular senescence by degrading PPARΓ expression. Taken together, our data show that E2 could upregulate SIRT1 expression via promoting the PPARΓ ubiquitination-proteasome degradation pathway to delay the process of cell senescence.
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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.