ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.
ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.
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ANP32B 介导的 p53 抑制有助于维持正常干细胞和 CML 干细胞。
作者：
Yang S;Zhu XN;Zhang HL;Yang Q;Wei YS;Zhu D;Liu MD;Shen SM;Xia L;He P;Ge MK;Pan YL;Zhao M;Wu YL;Zheng JK;Chen GQ;Yu Y
p53信号的适当调节对于造血干细胞（HSC）和白血病干细胞（LSC）的维持至关重要。调节p53活性的造血细胞特异性机制在很大程度上仍然未知。在这里，我们证明了造血细胞中富含酸性亮氨酸的核磷蛋白32B（ANP32B）的条件性缺失会损害造血干细胞的再增殖能力和损伤后再生。机制上，ANP32B与造血细胞中的p53形成抑制性复合物，从而抑制p53的转录活性，并且p53缺失挽救了Anp32b缺陷型HSC中的功能缺陷。令人感兴趣的是，ANP32B在来自慢性髓性白血病（CML）患者的白血病细胞中高度表达。在小鼠CML模型中，Anp32b缺失增强p53转录活性以损害LSC功能，并且在抑制CML增殖方面与酪氨酸激酶抑制剂表现出协同治疗作用。总之，我们的研究结果提供了一种通过抑制ANP32B来增强LSC中p53活性的新策略，并将ANP32B确定为治疗CML的潜在治疗靶点。
Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and post-injury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from chronic myelogenous leukemia (CML) patients. Anp32b deletion enhances p53 transcriptional activity to impair LSCs function in a murine CML model, and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B, and identify ANP32B as a potential therapeutic target in treating CML.
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影响因子：
8
作者：
Gen Sheng Wu;Timothy F Burns;E Robert McDonald III;Ray Meng;G. Kao;R. Muschel;T. Yen;W. El-Deiry
通讯作者：
Gen Sheng Wu;Timothy F Burns;E Robert McDonald III;Ray Meng;G. Kao;R. Muschel;T. Yen;W. El-Deiry
影响因子：
10.1
作者：
I. Veneziani;Paola Infante;E. Ferretti;O. Melaiu;Cecilia Battistelli;V. Lucarini;M. Compagnone;C. Nicoletti;A. Castellano;S. Petrini;M. Ognibene;A. Pezzolo;L. Di Marcotullio;R. Bei;L. Moretta;V. Pistoia;D. Fruci;V. Barnaba;F. Locatelli;L. Cifaldi
通讯作者：
I. Veneziani;Paola Infante;E. Ferretti;O. Melaiu;Cecilia Battistelli;V. Lucarini;M. Compagnone;C. Nicoletti;A. Castellano;S. Petrini;M. Ognibene;A. Pezzolo;L. Di Marcotullio;R. Bei;L. Moretta;V. Pistoia;D. Fruci;V. Barnaba;F. Locatelli;L. Cifaldi
影响因子：
5.6
作者：
Asai, Takashi;Liu, Yan;Bae, Narae;Nimer, Stephen D.
通讯作者：
Nimer, Stephen D.
靶向 USP47 克服酪氨酸激酶抑制剂耐药性并根除慢性粒细胞白血病中的白血病干/祖细胞
影响因子：
16.6
作者：
Lei H;Xu HZ;Shan HZ;Liu M;Lu Y;Fang ZX;Jin J;Jing B;Xiao XH;Gao SM;Gao FH;Xia L;Yang L;Liu LG;Wang WW;Liu CX;Tong Y;Wu YZ;Zheng JK;Chen GQ;Zhou L;Wu YL
通讯作者：
Wu YL
影响因子：
23.9
作者：
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD
通讯作者：
Nimer SD