title: p53 regulates hematopoietic stem cell quiescence.
abstract: The importance of the p53 protein in the cellular response to DNA damage is well known, but its function during steady-state hematopoiesis has not been established. We have defined a critical role of p53 in regulating hematopoietic stem cell quiescence, especially in promoting the enhanced quiescence seen in HSCs that lack the MEF/ELF4 transcription factor. Transcription profiling of HSCs isolated from wild-type and p53 null mice identified Gfi-1 and Necdin as p53 target genes, and using lentiviral vectors to upregulate or knockdown the expression of these genes, we show their importance in regulating HSC quiescence. Establishing the role of p53 (and its target genes) in controlling the cell-cycle entry of HSCs may lead to therapeutic strategies capable of eliminating quiescent cancer (stem) cells.
authors.affiliation: Molecular Phamacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Elf
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Goro
authors.initials: G
authors.lastname: Sashida
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Silvana
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Lee
authors.forename: Anthony
authors.initials: A
authors.lastname: Deblasio
authors.forename: Silvia
authors.initials: S
authors.lastname: Menendez
authors.forename: Jack
authors.initials: J
authors.lastname: Antipin
authors.forename: Boris
authors.initials: B
authors.lastname: Reva
authors.forename: Andrew
authors.initials: A
authors.lastname: Koff
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; C079873:Gfi1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C069766:necdin