The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans
Open Access
- 20 December 2012
- journal article
- review article
- Published by American Society of Hematology in Blood
- Vol. 120 (26), 5118-5127
- https://doi.org/10.1182/blood-2012-05-356014
Abstract
Aberrations in the p53 tumor suppressor pathway are associated with hematologic malignancies. p53-dependent cell cycle control, senescence, and apoptosis functions are actively involved in maintaining hematopoietic homeostasis under normal and stress conditions. Whereas loss of p53 function promotes leukemia and lymphoma development in humans and mice, increased p53 activity inhibits hematopoietic stem cell function and results in myelodysplasia. Thus, exquisite regulation of p53 activity is critical for homeostasis. Most of our understanding of p53 function in hematopoiesis is derived from genetically engineered mice. Here we summarize some of these models, the various mechanisms that disrupt the regulation of p53 activity, and their relevance to human disease.Keywords
This publication has 129 references indexed in Scilit:
- Rpl27a mutation in the sooty foot ataxia mouse phenocopies high p53 mouse modelsThe Journal of Pathology, 2011
- A High-Frequency Regulatory Polymorphism in the p53 Pathway Accelerates Tumor DevelopmentCancer Cell, 2010
- p53-Mediated Hematopoietic Stem and Progenitor Cell CompetitionCell Stem Cell, 2010
- Ribosomal protein S3: A multi-functional protein that interacts with both p53 and MDM2 through its KH domainDNA Repair, 2009
- The Tumor Suppressor p53 Regulates Polarity of Self-Renewing Divisions in Mammary Stem CellsCell, 2009
- Ribosomal Protein S7 Is Both a Regulator and a Substrate of MDM2Molecular Cell, 2009
- Increased Radioresistance and Accelerated B Cell Lymphomas in Mice with Mdmx Mutations that Prevent Modifications by DNA-Damage-Activated KinasesCancer Cell, 2009
- p53 Regulates Hematopoietic Stem Cell QuiescenceCell Stem Cell, 2009
- Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null miceExperimental Hematology, 2008
- Mdm2 Regulates p53 mRNA Translation through Inhibitory Interactions with Ribosomal Protein L26Molecular Cell, 2008