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The p53 tumour suppressor inhibits glucocorticoid‐induced proliferation of erythroid progenitors
Author(s) -
Ganguli Gitali,
Back Jonathan,
Sengupta Sagar,
Wasylyk Bohdan
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf114
Subject(s) - erythropoiesis , haematopoiesis , biology , progenitor cell , glucocorticoid receptor , glucocorticoid , population , endocrinology , medicine , cancer research , stem cell , microbiology and biotechnology , anemia , environmental health
Hypoxia encountered at high altitude, blood loss and erythroleukemia instigate stress erythropoiesis, which involves glucocorticoid‐induced proliferation of erythroid progenitors (ebls). The tumour suppressor p53 stimulates hematopoietic cell maturation and antagonizes glucocorticoid receptor (GR) activity in hypoxia, suggesting that it may inhibit stress erythropoiesis. We report that mouse fetal liver ebls that lack p53 proliferate better than wild‐type cells in the presence of the GR agonist dexamethasone. An important mediator of GR‐induced ebl self‐renewal, the c‐ myb gene, is induced to higher levels in p53 −/− ebls by dexamethasone. The stress response to anemia is faster in the spleens of p53 −/− mice, as shown by the higher levels of colony forming units erythroids and the increase in the CD34/c‐kit double positive population. Our results show that p53 antagonizes GR‐mediated ebl expansion and demonstrate for the first time that p53–GR cross‐talk is important in a physiological process in vivo : stress erythropoiesis.