title: The p53 tumor suppressor protein is a critical regulator of hematopoietic stem cell behavior.
abstract: In response to diverse stresses, the tumor suppressor p53 differentially regulates its target genes, variably inducing cell-cycle arrest, apoptosis or senescence. Emerging evidence indicates that p53 plays an important role in regulating hematopoietic stem cell (HSC) quiescence, self-renewal, apoptosis and aging. The p53 pathway is activated by DNA damage, defects in ribosome biogenesis, oxidative stress and oncogene induced p19 ARF upregulation. We present an overview of the current state of knowledge about p53 (and its target genes) in regulating HSC behavior, with the hope that understanding the molecular mechanisms that control p53 activity in HSCs and how p53 mutations affect its role in these events may facilitate the development of therapeutic strategies for eliminating leukemia (and cancer) propagating cells.
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Elf
authors.forename: Takashi
authors.initials: T
authors.lastname: Asai
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Goro
authors.initials: G
authors.lastname: Sashida
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Silvana
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: Andrew
authors.initials: A
authors.lastname: Koff
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D016922:Cellular Senescence; D004249:DNA Damage; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2