ArticleProceedings of the National Academy of Sciences of the United States of America2013
REGγ deficiency promotes premature aging via the casein kinase 1 pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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
44 citing papers in PubMed, 74 citations in OpenAlex.
- Associations between proteasomal activator PA28γ and outcome of oral squamous cell carcinoma: Evidence from cohort studies and functional analyses.EBioMedicine · 2015Trial
- NRF2-REGγ-ACADM/KLF15 Signaling Pathway Regulates the Browning of White Adipose Tissue to Modulate Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitin-independent pathway regulates the RIT1-MAPK pathway in chordoma progression.Cell death & disease · 2025Article
- REGγ regulates antiviral response by activating TBK1-IFNβ signaling through degradation of PPP2CB.Cellular and molecular life sciences : CMLS · 2025Article
- REGγ is essential to maintain bone homeostasis by degrading TRAF6, preventing osteoporosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- REGγ deficiency ameliorates hepatic ischemia and reperfusion injury in a mitochondrial p66shc dependent manner in mice.Translational gastroenterology and hepatology · 2024Article
- Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.Frontiers in immunology · 2024Article
- USP13 regulates cell senescence through mediating MDM2 stability.Life sciences · 2023Article
- Reciprocal REGOxidative medicine and cellular longevity · 2023Article
- Regulation of Life & Death by REGγ.Cells · 2022Review
- REGγ regulates circadian clock by modulating BMAL1 protein stability.Cell death discovery · 2021Article
- The proteasome activator REGγ accelerates cardiac hypertrophy by declining PP2Acα-SOD2 pathway.Cell death and differentiation · 2020Article
- SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.The EMBO journal · 2020Article
- The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells.Nature communications · 2020Article
- REG γ knockdown suppresses proliferation by inducing apoptosis and cell cycle arrest in osteosarcoma.PeerJ · 2020Article
- The oncogenic role of REG γ is exerted by activating the Wnt/β-catenin signaling pathway in osteosarcoma.American journal of translational research · 2020Article
- Review
- The REGγ-Proteasome Regulates Spermatogenesis Partially by P53-PLZF Signaling.Stem cell reports · 2019Article
- Expression of REGγ in atherosclerotic plaques and promotes endothelial cells apoptosis via the cyclophilin A pathway indicates functional implications in atherogenesis.Cell cycle (Georgetown, Tex.) · 2019Article
Corrections and comments
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Authors and funding
27 authors at 5 institutions in 3 countries.
Funding
Abstract
Our recent studies suggest a role for the proteasome activator REG (11S regulatory particles, 28-kDa proteasome activator)γ in the regulation of tumor protein 53 (p53). However, the molecular details and in vivo biological significance of REGγ-p53 interplay remain elusive. Here, we demonstrate that REGγ-deficient mice develop premature aging phenotypes that are associated with abnormal accumulation of casein kinase (CK) 1δ and p53. Antibody array analysis led us to identify CK1δ as a direct target of REGγ. Silencing CK1δ or inhibition of CK1δ activity prevented decay of murine double minute (Mdm)2. Interestingly, a massive increase of p53 in REGγ(-/-) tissues is associated with reduced Mdm2 protein levels despite that Mdm2 transcription is enhanced. Allelic p53 haplodeficiency in REGγ-deficient mice attenuated premature aging features. Furthermore, introducing exogenous Mdm2 to REGγ(-/-) MEFs significantly rescues the phenotype of cellular senescence, thereby establishing a REGγ-CK1-Mdm2-p53 regulatory pathway. Given the conflicting evidence regarding the "antiaging" and "proaging" effects of p53, our results indicate a key role for CK1δ-Mdm2-p53 regulation in the cellular aging process. These findings reveal a unique model that mimics acquired aging in mammals and indicates that modulating the activity of the REGγ-proteasome may be an approach for intervention in aging-associated disorders.
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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.