ArticleCell reports2014
The multifunctional sorting protein PACS-2 regulates SIRT1-mediated deacetylation of p53 to modulate p21-dependent cell-cycle arrest.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Pooled it
- PACS1 syndrome variant alters the proteomic landscape of developing cortical organoids.iScience · 2026Article
- Is the Loss of Previously Acquired Skills a Feature of PACS1-, PACS2- and WDR37-Related Syndromes? A Systematized Narrative Review.International journal of molecular sciences · 2026Review
- PACS2 at Mitochondria-Associated Membranes: A Central Regulator of Cardiovascular and Metabolic Diseases.Journal of cellular and molecular medicine · 2026Review
- Identification of MKRN1 as a key modulator of the p53-MDM2 feedback loop.Cell death and differentiation · 2026Article
- Phosphofurin Acidic Cluster Sorting Protein 2 Alleviates Kidney Fibrosis by Inhibiting Tubular Epithelial Cell G2/M Arrest through Cyclin-Dependent Kinase-Like 1.Journal of the American Society of Nephrology : JASN · 2026Article
- Macrophage FTO deficiency accelerates atherosclerosis via PACS2-mediated activation of the PPARγ lipid signaling pathway.Journal of translational medicine · 2026Article
- PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2.Communications biology · 2026Article
- Understanding PACS2 syndrome's pathomechanism by studying E209K and E211K mutations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells.Journal of ovarian research · 2025Article
- Inhibitory protein-protein interactions of the SIRT1 deacetylase are choreographed by post-translational modification.Protein science : a publication of the Protein Society · 2024Article
- NAD metabolism: Role in senescence regulation and aging.Aging cell · 2024Review
- SIRT1 is an actionable target to restore p53 function in HPV-associated cancer therapy.British journal of cancer · 2023Article
- Neural deficits in a mouse model of PACS1 syndrome are corrected with PACS1- or HDAC6-targeting therapy.Nature communications · 2023Article
- PACS-2 deficiency aggravates tubular injury in diabetic kidney disease by inhibiting ER-phagy.Cell death & disease · 2023Article
- Insights into Regulators of p53 Acetylation.Cells · 2022Review
- The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.ACS omega · 2022Article
- Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing.Nature communications · 2022Article
- WDR37 syndrome: identification of a distinct new cluster of disease-associated variants and functional analyses of mutant proteins.Human genetics · 2021Article
- PACS-2 attenuates diabetic kidney disease via the enhancement of mitochondria-associated endoplasmic reticulum membrane formation.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
SIRT1 regulates the DNA damage response by deacetylating p53, thereby repressing p53 transcriptional output. Here, we demonstrate that the sorting protein PACS-2 regulates SIRT1-mediated deacetylation of p53 to modulate the DNA damage response. PACS-2 knockdown cells failed to efficiently undergo p53-induced cell-cycle arrest in response to DNA damage. Accordingly, p53 acetylation was reduced both in PACS-2 knockdown cells and thymocytes from Pacs-2(-/-) mice, thereby blunting induction of the cyclin-dependent kinase inhibitor p21 (CDKN1A). The SIRT1 inhibitor EX-527 or SIRT1 knockdown restored p53 acetylation and p21 induction as well as p21-dependent cell-cycle arrest in PACS-2 knockdown cells. Trafficking studies revealed that cytoplasmic PACS-2 shuttled to the nucleus, where it interacted with SIRT1 and repressed SIRT1-mediated p53 deacetylation. Correspondingly, in vitro assays demonstrated that PACS-2 directly inhibited SIRT1-catalyzed p53 deacetylation. Together, these findings identify PACS-2 as an in vivo mediator of the SIRT1-p53-p21 axis that modulates the DNA damage response.
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