自噬
生物
单核细胞
细胞生物学
髓样
ULK1
细胞分化
巨噬细胞
髓系白血病
癌症研究
受体
安普克
免疫学
激酶
细胞凋亡
蛋白激酶A
遗传学
体外
基因
作者
Sandrine Obba,Zoheir Hizir,Laurent Boyer,Dorothée Selimoglu‐Buet,Anja Pfeifer,Grégory Michel,Mohamed-Amine Hamouda,Diogo Gonçalvès,Michaël Cerezo,Sandrine Marchetti,Stéphane Rocchi,Nathalie Droin,Thomas Cluzeau,Guillaume Robert,Frédéric Luciano,Bernard Robaye,Marc Foretz,Benoı̂t Viollet,Laurence Legros,Éric Solary,Patrick Auberger,Arnaud Jacquel
出处
期刊:Autophagy
[Informa]
日期:2015-07-03
卷期号:11 (7): 1114-1129
被引量:89
标识
DOI:10.1080/15548627.2015.1034406
摘要
Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.
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