ArticleMolecular and cellular biology2012
A deacetylase-deficient SIRT1 variant opposes full-length SIRT1 in regulating tumor suppressor p53 and governs expression of cancer-related genes.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Factors Determining Sirtuin-1 Target Engagement.Advanced biology · 2026Review
- The Role of Sirtuin-1 Isoforms in Regulating Mitochondrial Function.Current issues in molecular biology · 2024Article
- Ameliorative effects of bilirubin on cell culture model of non-alcoholic fatty liver disease.Molecular biology reports · 2023Article
- Splicing alterations in healthy aging and disease.Wiley interdisciplinary reviews. RNA · 2021Review
- Angiotensin II type 1 receptor-associated protein deficiency attenuates sirtuin1 expression in an immortalised human renal proximal tubule cell line.Scientific reports · 2019Article
- Catalytic-independent neuroprotection by SIRT1 is mediated through interaction with HDAC1.PloS one · 2019Article
- Detection of Sirtuin-1 protein expression in peripheral blood leukocytes in dogs.The Journal of veterinary medical science · 2018Article
- SIRT1 Is a Potential Drug Target for Treatment of Diabetic Kidney Disease.Frontiers in endocrinology · 2018Review
- p53 inhibits the upregulation of sirtuin 1 expression induced by c-Myc.Oncology letters · 2017Article
- Identification of a Tissue-Restricted Isoform of SIRT1 Defines a Regulatory Domain that Encodes Specificity.Cell reports · 2017Article
- Article
- HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA.International journal of molecular sciences · 2014Article
- RNA Interference by Single- and Double-stranded siRNA With a DNA Extension Containing a 3' Nuclease-resistant Mini-hairpin Structure.Molecular therapy. Nucleic acids · 2014Article
- Recreational scuba diving: negative or positive effects of oxidative and cardiovascular stress?Biochemia medica · 2014Review
- Deacetylase-independent function of HDAC3 in transcription and metabolism requires nuclear receptor corepressor.Molecular cell · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SIRT1 is an NAD-dependent deacetylase and epigenetic regulator essential for normal mammalian development and homeostasis. Here we describe a human SIRT1 splice variant, designated SIRT1-Δ2/9, in which the deacetylase coding sequence is lost due to splicing between exons 2 and 9. This work aimed to determine if SIRT1-Δ2/9 is a novel functional product of the SIRT1 gene. Endogenous SIRT1-Δ2/9 protein was identified in human cell lysate by immunoblotting and splice variant-specific RNA interference (RNAi). SIRT1-Δ2/9 mRNA is bound by CUGBP2, which downregulates its translation. Using pulldown assays, we demonstrate that SIRT1-Δ2/9 binds p53 protein. SIRT1-Δ2/9 maintains basal p53 protein levels and supports p53 function in response to DNA damage, as evidenced by RNAi-mediated depletion of SIRT1-Δ2/9 prior to damage. In turn, basal p53 downregulates SIRT1-Δ2/9 RNA levels, while stress-activated p53 eliminates SIRT1-Δ2/9. Loss of wild-type (wt) p53 has been correlated with overexpression of SIRT1-Δ2/9 in a range of human cancers. Exogenous SIRT1-Δ2/9 protein associates with specific promoters in chromatin and can regulate cancer-related gene expression, as evidenced by chromatin immunoprecipitation analysis and RNAi/genomic array data. SIRT1 is of major therapeutic importance, and potential therapeutic drugs are screened against SIRT1 deacetylase activity. Our discovery of SIRT1-Δ2/9 identifies a new, deacetylase-independent therapeutic target for SIRT1-related diseases, including cancer.
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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.