The p53 tumor suppressor protein regulates hematopoietic stem cell fate.
The p53 tumor suppressor protein regulates hematopoietic stem cell fate.
复制标题
DOI：
10.1002/jcp.22561
复制
发表时间：
2011-09
影响因子：
5.6
通讯作者：
Nimer, Stephen D.
中科院分区：
文献类型：
--
作者：
Asai, Takashi;Liu, Yan;Bae, Narae;Nimer, Stephen D.
p53肿瘤抑制蛋白是一个关键的转录因子，调节参与细胞对应激反应的几个信号通路。通过应激诱导的激活，p53积累并触发靶基因的表达，保护包括造血干细胞（HSC）在内的所有细胞的遗传完整性。这些保护机制包括细胞周期停滞、DNA修复、诱导凋亡或启动衰老。除了在应激条件下的功能外，p53在稳态造血过程中具有重要功能，调节HSC静止和自我更新。此外，似乎p53水平影响HSC对造血生态位的竞争，p53活化较少的HSC优先存活。p53对正常HSC作用的具体基因和确切机制正在慢慢澄清。p53在白血病干细胞（LSC）行为中也起着重要作用，p53缺失影响耐药性和疾病进展。药理学激活p53功能可以克服LSC中p53失活的不利影响。因此，了解p53在HSC和LSC中的调节机制可能会促进新的治疗策略的发展，这些策略可以消除大量静止的LSC。
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.
登录
查看更多内容
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1073/pnas.88.14.6293
发表时间：
1991-07-01
影响因子：
11.1
作者：
FEINSTEIN, E;CIMINO, G;CANAANI, E
通讯作者：
CANAANI, E
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
10.5
作者：
CANMAN, CE;GILMER, TM;KASTAN, MB
通讯作者：
KASTAN, MB
影响因子：
10.5
作者：
Bender, CF;Sikes, ML;Petrini, JHJ
通讯作者：
Petrini, JHJ