title: Induction of the autophagy-associated gene MAP1S via PU.1 supports APL differentiation.
abstract: The PU.1 transcription factor is essential for myeloid development. We investigated if the microtubule-associated protein 1S (MAP1S) is a novel PU.1 target with a link to autophagy, a cellular recycling pathway. Comparable to PU.1, MAP1S expression was significantly repressed in primary AML blasts as compared to mature neutrophils. Accordingly, MAP1S expression was induced during neutrophil differentiation of CD34(+) progenitor and APL cells. Moreover, PU.1 bound to the MAP1S promoter and induced MAP1S expression during APL differentiation. Inhibiting MAP1S resulted in aberrant neutrophil differentiation and autophagy. Taken together, our findings implicate the PU.1-regulated MAP1S gene in neutrophil differentiation and autophagy control.
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
authors.forename: Aladin
authors.initials: A
authors.lastname: Haimovici
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brigger
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Torbett
authors.affiliation: Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fey
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland; Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland. Electronic address: mtschan@pathology.unibe.ch.
authors.forename: Mario P
authors.initials: MP
authors.lastname: Tschan
mesh_terms: D001343:Autophagy / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007231:Infant, Newborn; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C493240:MAP1S protein, human
keywords: Acute promyelocytic leukemia; All-trans retinoic acid (ATRA); Autophagy; MAP1S; Neutrophil; PU.1