title: hnRNP K in PU.1-containing complexes recruited at the CD11b promoter: a distinct role in modulating granulocytic and monocytic differentiation of AML-derived cells.
abstract: PU.1 is essential for the differentiation of haemopoietic precursors and is strongly implicated in leukaemogenesis, yet the protein interactions that regulate its activity in different myeloid lineages are still largely unknown. In the present study, by combining fluorescent EMSA (electrophoretic mobility-shift assay) with MS, we reveal the presence of hnRNP K (heterogeneous nuclear ribonucleoprotein K) in molecular complexes that PU.1 forms on the CD11b promoter during the agonist-induced maturation of AML (acute myeloid leukaemia)-derived cells along both the granulocytic and the monocytic lineages. Although hnRNP K and PU.1 act synergistically during granulocytic differentiation, hnRNP K seems to have a negative effect on PU.1 activity during monocytic maturation. Since hnRNP K acts as a docking platform, integrating signal transduction pathways to nucleic acid-directed processes, it may assist PU.1 in activating or repressing transcription by recruiting lineage-specific components of the transcription machinery. It is therefore possible that hnRNP K plays a key role in the mechanisms underlying the specific targeting of protein-protein interactions identified as mediators of transcriptional activation or repression and may be responsible for the block of haemopoietic differentiation.
authors.affiliation: *Section of Anatomy and Histology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Ervin
authors.initials: E
authors.lastname: Nika
authors.affiliation: *Section of Anatomy and Histology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Brugnoli
authors.affiliation: †Cell Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Piazzi
authors.affiliation: ‡Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lambertini
authors.affiliation: *Section of Anatomy and Histology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Grassilli
authors.affiliation: §SC Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bavelloni
authors.affiliation: ‡Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Piva
authors.forename: Silvano
authors.initials: S
authors.lastname: Capitani
authors.affiliation: *Section of Anatomy and Histology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertagnolo
mesh_terms: D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006098:Granulocytes / Q000378:metabolism* / Q000473:pathology; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D039481:CD11b Antigen; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D011518:Proto-Oncogene Proteins; D012261:Ribonucleoproteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C509295:ITGAM protein, human; C072074:HNRNPK protein, human