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Regulation of hematopoietic stem cell integrity through p53 and its related factors
Author(s) -
Yamashita Masayuki,
Nitta Eriko,
Suda Toshio
Publication year - 2016
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12986
Subject(s) - haematopoiesis , microbiology and biotechnology , apoptosis , stem cell , dna damage , biology , hematopoietic stem cell , mutagenesis , dna repair , programmed cell death , mutation , cancer research , dna , genetics , gene
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.