p53 regulates hematopoietic stem cell quiescence
| Autor: | Boris Reva, Goro Sashida, Anthony DeBlasio, Andrew Koff, Silvana Di Giandomenico, Yasuhiko Miyata, Gang Huang, Shannon Elf, Jack Antipin, Yan Liu, Yuhui Liu, Jennifer May Lee, Stephen D. Nimer, Silvia Menendez |
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| Rok vydání: | 2008 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male Tumor suppressor gene Transcription Genetic Nerve Tissue Proteins CELLCYCLE Biology 03 medical and health sciences Mice 0302 clinical medicine medicine Genetics Animals Transcription factor 030304 developmental biology Cell Proliferation Mice Knockout 0303 health sciences Gene knockdown Cell growth Cell Cycle Hematopoietic stem cell Nuclear Proteins Cell Biology Cell cycle Hematopoietic Stem Cells STEMCELL Hematopoiesis DNA-Binding Proteins Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Molecular Medicine Female Stem cell Tumor Suppressor Protein p53 Transcription Factors |
| Zdroj: | Cell stem cell. 4(1) |
| ISSN: | 1875-9777 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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