ArticleCell death and differentiation2016
Repression of p53-target gene Bbc3/PUMA by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Advances in the Regulation of Hematopoietic Homeostasis by Programmed Cell Death Under Radiation Conditions.Stem cell reviews and reports · 2025Pooled it
- PUMA-induced apoptosis drives bone marrow failure and genomic instability in telomerase-deficient mice.Cell death and differentiation · 2026Article
- Review
- Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways.Cancer cell international · 2025Article
- Deubiquitinase MYSM1 promotes doxorubicin-induced cardiotoxicity by mediating TRIM21-ferroptosis axis in cardiomyocytes.Cell communication and signaling : CCS · 2024Article
- Deubiquitinase MYSM1: An Important Tissue Development and Function Regulator.International journal of molecular sciences · 2024Review
- Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis.Cell communication and signaling : CCS · 2024Article
- Sequence-to-expression approach to identify etiological non-coding DNA variations in P53 and cMYC-driven diseases.Human molecular genetics · 2024Article
- MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.The Journal of allergy and clinical immunology · 2024Article
- Deubiquitinase Mysm1 regulates neural stem cell proliferation and differentiation by controlling Id4 expression.Cell death & disease · 2024Article
- Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo.Biomedicines · 2023Article
- MYSM1 induces apoptosis and sensitizes TNBC cells to cisplatin via RSK3-phospho-BAD pathway.Cell death discovery · 2022Article
- p53-dependent induction of P2X7 on hematopoietic stem and progenitor cells regulates hematopoietic response to genotoxic stress.Cell death & disease · 2021Article
- Puma- and Caspase9-mediated apoptosis is dispensable for p53-driven neural crest-based developmental defects.Cell death and differentiation · 2021Article
- RIPK1 Coordinates Bone Marrow Mesenchymal Stem Cell Survival by Maintaining Mitochondrial Homeostasis via p53.Stem cells international · 2021Article
- Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1.Frontiers in immunology · 2021Article
- MYSM1 Suppresses Cellular Senescence and the Aging Process to Prolong Lifespan.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- MYSM1 maintains ribosomal protein gene expression in hematopoietic stem cells to prevent hematopoietic dysfunction.JCI insight · 2020Article
- Interaction of Deubiquitinase 2A-DUB/MYSM1 with DNA Repair and Replication Factors.International journal of molecular sciences · 2020Article
- Deubiquitinase MYSM1 in the Hematopoietic System and beyond: A Current Review.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
p53 is a central mediator of cellular stress responses, and its precise regulation is essential for the normal progression of hematopoiesis. MYSM1 is an epigenetic regulator essential for the maintenance of hematopoietic stem cell (HSC) function, hematopoietic progenitor survival, and lymphocyte development. We recently demonstrated that all developmental and hematopoietic phenotypes of Mysm1 deficiency are p53-mediated and rescued in the Mysm1(-/-)p53(-/-) mouse model. However, the mechanisms triggering p53 activation in Mysm1(-/-) HSPCs, and the pathways downstream of p53 driving different aspects of the Mysm1(-/-) phenotype remain unknown. Here we show the transcriptional activation of p53 stress responses in Mysm1(-/-) HSPCs. Mechanistically, we find that the MYSM1 protein associates with p53 and colocalizes to promoters of classical p53-target genes Bbc3/PUMA (p53 upregulated modulator of apoptosis) and Cdkn1a/p21. Furthermore, it antagonizes their p53-driven expression by modulating local histone modifications (H3K27ac and H3K4me3) and p53 recruitment. Using double-knockout mouse models, we establish that PUMA, but not p21, is an important mediator of p53-driven Mysm1(-/-) hematopoietic dysfunction. Specifically, Mysm1(-/-)Puma(-/-) mice show full rescue of multipotent progenitor (MPP) viability, partial rescue of HSC quiescence and function, but persistent lymphopenia. Through transcriptome analysis of Mysm1(-/-)Puma(-/-) MPPs, we demonstrate strong upregulation of other p53-induced mediators of apoptosis and cell-cycle arrest. The full viability of Mysm1(-/-)Puma(-/-) MPPs, despite strong upregulation of many other pro-apoptotic mediators, establishes PUMA as the essential non-redundant effector of p53-induced MPP apoptosis. Furthermore, we identify potential mediators of p53-dependent but PUMA-independent Mysm1(-/-)hematopoietic deficiency phenotypes. Overall, our study provides novel insight into the cell-type-specific roles of p53 and its downstream effectors in hematopoiesis using unique models of p53 hyperactivity induced by endogenous stress. We conclude that MYSM1 is a critical negative regulator of p53 transcriptional programs in hematopoiesis, and that its repression of Bbc3/PUMA expression is essential for MPP survival, and partly contributes to maintaining HSC function.
Indexed as
Identifiers
What OpenQuestion holds
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.