ArticlePLoS biology2016
Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Genetic heterogeneity and homogeneity among orofacial cleft subtypes: genome-wide association studies in the cleft collective.Human molecular genetics · 2025Pooled it
- An optimised promoter and signal peptide improves methionine production of a genetically engineeredFrontiers in microbiology · 2025Article
- Hepatic depletion of nucleolar protein mDEF causes excessive mitochondrial copper accumulation associated with p53 and NRF1 activation.iScience · 2023Article
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- Loss ofGenes · 2023Article
- Bulk RNA-seq and scRNA-seq analysis reveal an activation of immune response and compromise of secretory function in major salivary glands of obese mice.Computational and structural biotechnology journal · 2023Article
- Calpain signaling: from biology to therapeutic opportunities in neurodegenerative disorders.Frontiers in veterinary science · 2023Review
- Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances.Archives of microbiology · 2022Review
- Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication.Journal of molecular cell biology · 2022Article
- Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.Scientific reports · 2021Article
- Rcl1 depletion impairs 18S pre-rRNA processing at the A1-site and up-regulates a cohort of ribosome biogenesis genes in zebrafish.Nucleic acids research · 2021Article
- Article
- Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish.Cell death & disease · 2021Article
- Effects of functionally diverse calpain system on immune cells.Immunologic research · 2021Review
- All routes lead to Rome: multifaceted origin of hepatocytes during liver regeneration.Cell regeneration (London, England) · 2021Review
- BLM interaction with EZH2 regulates MDM2 expression and is a poor prognostic biomarker for prostate cancer.American journal of cancer research · 2021Article
- Capn3 depletion causes Chk1 and Wee1 accumulation and disrupts synchronization of cell cycle reentry during liver regeneration after partial hepatectomy.Cell regeneration (London, England) · 2020Article
- Zebrafish hhex-null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1.Journal of molecular cell biology · 2019Article
- Sas10 controls ribosome biogenesis by stabilizing Mpp10 and delivering the Mpp10-Imp3-Imp4 complex to nucleolus.Nucleic acids research · 2019Article
- Screening for implicated genes in colorectal cancer using whole‑genome gene expression profiling.Molecular medicine reports · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis.
Identifiers
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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.