The p53 tumor suppressor protein regulates hematopoietic stem cell fate Journal Article


Authors: Asai, T.; Liu, Y.; Bae, N.; Nimer, S. D.
Article Title: The p53 tumor suppressor protein regulates hematopoietic stem cell fate
Abstract: The p53 tumor suppressor protein is a key transcription factor that regulates several signaling pathways involved in the cell's response to stress. Through stress-induced activation, p53 accumulates and triggers the expression of target genes that protect the genetic integrity of all cells including hematopoietic stem cells (HSCs). These protective mechanisms include cell-cycle arrest, DNA repair, induction of apoptosis, or initiation of senescence. In addition to its function under stress conditions, p53 has important functions during steady-state hematopoiesis, regulating HSC quiescence and self-renewal. In addition, it appears that p53 levels affect HSC competition for the hematopoietic niche, with the less p53 activated HSCs preferentially surviving. The specific genes and precise mechanisms underlying p53's effects on normal HSCs are slowly being clarified. p53 also plays an important role in leukemia stem cell (LSC) behavior, with p53 loss affecting drug resistance and disease progression. Pharmacologic activation of p53 function could overcome the adverse impact of p53 inactivation in LSCs. Thus, understanding the p53 regulatory mechanisms active in HSCs and LSCs may promote the development of new therapeutic strategies that could eliminate the population of largely quiescent LSCs. © 2010 Wiley-Liss, Inc.
Keywords: leukemia; nonhuman; protein function; cell proliferation; cell survival; dna repair; apoptosis; gene expression; steady state; cell fate; cell renewal; protein p53; cancer stem cell; cell cycle arrest; short survey; hematopoiesis; hematopoietic stem cell; senescence; bone marrow transplantation; cell activation; cell protection; cell aging; cell stress
Journal Title: Journal of Cellular Physiology
Volume: 226
Issue: 9
ISSN: 0021-9541
Publisher: John Wiley & Sons, Inc.  
Date Published: 2011-09-01
Start Page: 2215
End Page: 2221
Language: English
DOI: 10.1002/jcp.22561
PROVIDER: scopus
PUBMED: 21660944
PMCID: PMC3081536
DOI/URL:
Notes: --- - "Export Date: 17 August 2011" - "CODEN: JCLLA" - "Source: Scopus"
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  1. Stephen D Nimer
    347 Nimer
  2. Takashi Asai
    12 Asai
  3. Yan Liu
    23 Liu
  4. Narae Bae
    4 Bae