title: [Maintenance of hematopoietic stem cell integrity and regulation of leukemogenesis by p53 and its coactivator Aspp1].
abstract: Hematopoietic stem cells (HSCs) are predominantly in a quiescent state, thereby avoiding depletion due to various stresses. However, quiescent HSCs are vulnerable to mutagenesis due to low-fidelity DNA repair. The mechanism by which HSCs avoid mutation accumulation remains to be elucidated. HSCs are normally resistant to apoptosis because of their abundant expressions of pro-survival Bcl-2 family genes. In contrast, p53 is activated in HSCs in response to DNA damage. We have recently shown that pro-apoptotic Bcl-2 signals are activated through p53 preferentially in HSCs with damaged DNA. Aspp1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and coordinates with p53 to maintain the genomic soundness of the HSC pool. In this review, we will summarize apoptosis regulation and the roles of p53 in HSCs, and introduce our findings showing coordinated regulations of HSC self-renewal, DNA damage tolerance and hematological malignancies by Aspp1 and p53.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Eriko
authors.initials: E
authors.lastname: Nitta
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C498406:PPP1R13B protein, human; D016159:Tumor Suppressor Protein p53