期刊
HEMATOPOIETIC STEM CELLS IX
卷 1370, 期 -, 页码 45-54出版社
BLACKWELL SCIENCE PUBL
DOI: 10.1111/nyas.12986
关键词
hematopoietic stem cells; BCL-2; p53; ASPP1; apoptosis; hematological malignancies
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- EU grant of SyStemAge
- Singapore NMRC grant of STaR Award
- Global COE program Education and Research Center for Stem Cell Medicine of Keio University
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [26221309] Funding Source: KAKEN
The majority of hematopoietic stem cells (HSCs) are maintained in a quiescent state to minimize premature exhaustion induced by various stresses. However, quiescent HSCs are vulnerable to mutagenesis because of attenuated DNA repair and DNA damage response programs. Basal abundant expression of prosurvival BCL-2 proteins further endows HSCs with high resistance to apoptosis. In contrast, HSCs elicit strong activation of p53 upon DNA damage, resulting in enhanced activation of proapoptotic BCL-2 signals through p53. ASPP1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and preserves HSC pool integrity via selective induction of apoptosis. In this paper, we discuss the role of p53 and mitochondrial apoptosis in HSC regulation and introduce the current understanding of how p53 activity is regulated to achieve a good balance between maintaining the HSC pool and preventing hematological malignancies.
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