title: Regulation of megakaryocytic differentiation of K562 cells by FosB, a member of the Fos family of AP-1 transcription factors.
abstract: The regulation of megakaryocytic differentiation is poorly understood. Using K562 cells, which can partly recapitulate the process in response to phorbol 12-myristate 13-acetate (PMA), we performed microarray-based gene expression profiling to identify genes that play significant roles in megakaryopoiesis. Here, we describe the function of FosB, an AP-1 transcription factor. FosB is induced in PMA treated K562 cells in a sustained manner and forms an active AP-1 protein-DNA complex. Down-regulation of FosB with specific shRNAs inhibited the induction of CD41, a specific cell surface marker of megakaryocytes. We also show that activation of the PKC-MEK-ERK signaling pathway is required for induction of FosB and CD41. Finally, we cross-examined the microarray data in conjunction with gene function annotation data to identify additional target genes of FosB. We define 3 genes, INHBA, CD9, and ITGA2B as regulatory targets of FosB and show that CD9, in particular, is a direct target of FosB.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
authors.forename: J-K
authors.initials: JK
authors.lastname: Limb
authors.forename: S
authors.initials: S
authors.lastname: Yoon
authors.forename: K E
authors.initials: KE
authors.lastname: Lee
authors.forename: B-H
authors.initials: BH
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: Y S
authors.initials: YS
authors.lastname: Bae
authors.forename: G-J
authors.initials: GJ
authors.lastname: Jhon
authors.forename: J
authors.initials: J
authors.lastname: Kim
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D028322:Inhibin-beta Subunits / Q000378:metabolism; D039421:Integrin alpha2 / Q000378:metabolism; D020014:K562 Cells; D020935:MAP Kinase Signaling System / Q000502:physiology; D008533:Megakaryocytes / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D060245:Tetraspanin 29; D018808:Transcription Factor AP-1 / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C554869:CD9 protein, human; C064269:FOSB protein, human; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D008562:Membrane Glycoproteins; D040201:Platelet Membrane Glycoprotein IIb; D016760:Proto-Oncogene Proteins c-fos; D060245:Tetraspanin 29; D018808:Transcription Factor AP-1; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate