The p53 tumor suppressor protein regulates hematopoietic stem cell fate

Takashi Asai, Yan Liu, Narae Bae, Stephen D. Nimer

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2215-2221
Number of pages7
JournalJournal of Cellular Physiology
Volume226
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

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Tumor Suppressor Protein p53
Hematopoietic Stem Cells
Stem cells
Genes
Chemical activation
Hematopoiesis
Cell Cycle Checkpoints
Drug Resistance
DNA Repair
Disease Progression
Leukemia
Transcription Factors
Stem Cells
Apoptosis
Repair
Gene Expression
Cells
DNA
Population
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

The p53 tumor suppressor protein regulates hematopoietic stem cell fate. / Asai, Takashi; Liu, Yan; Bae, Narae; Nimer, Stephen D.

In: Journal of Cellular Physiology, Vol. 226, No. 9, 09.2011, p. 2215-2221.

Research output: Contribution to journalArticle

Asai, Takashi ; Liu, Yan ; Bae, Narae ; Nimer, Stephen D. / The p53 tumor suppressor protein regulates hematopoietic stem cell fate. In: Journal of Cellular Physiology. 2011 ; Vol. 226, No. 9. pp. 2215-2221.
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