The ups and downs of p53 regulation in hematopoietic stem cells

被引：25

作者：

Abbas, Hussein A. ^{[1
]}

Pant, Vinod ^{[1
]}

Lozano, Guillermina ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA

来源：

CELL CYCLE | 2011年 / 10卷 / 19期

关键词：

HSC; reactive oxygen species; ROS; p53; Mdm2; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; C-KIT; MDM2; DIFFERENTIATION; SENESCENCE; RESCUE; ROS; TUMORIGENESIS; MAINTENANCE;

D O I：

10.4161/cc.10.19.17721

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hematopoietic stem cells provide an indispensible source for replenishing the blood with all its constituents throughout the organism's lifetime. Mice with a compromised hematopoietic stem cell compartment cannot survive. p53, a major tumor suppressor gene, has been implicated in regulation of hematopoiesis. In particular, p53 plays a role in homeostasis by regulating HSC quiescence and self renewal. We recently utilized a hypomorphic p53(515C) allele in conjunction with Mdm2, a negative regulator of p53, to gain insights into the role of p53 in hematopoietic regulation. Our analyses revealed that p53(515C/515C)Mdm2(-/-) double mutant mice die soon after birth due to hematopoietic failure. Further mechanistic studies revealed that in the absence of Mdm2, ROS-induced postnatal p53 activity depletes hematopoietic stem cells, progenitors and differentiated cells.

引用

页码：3257 / 3262

页数：6

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