title: Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation.
abstract: Sox2 is a pluripotency transcription factor that as an oncogene can also regulate cell proliferation. Therefore, genes implicated in several different aspects of cell proliferation, such as the VRK1 chromatin-kinase, are candidates to be targets of Sox2. Sox 2 and VRK1 colocalize in nuclei of proliferating cells forming a stable complex. Sox2 knockdown abrogates VRK1 gene expression. Depletion of either Sox2 or VRK1 caused a reduction of cell proliferation. Sox2 up-regulates VRK1 expression and both proteins cooperate in the activation of CCND1. The accumulation of VRK1 protein downregulates SOX2 expression and both proteins are lost in terminally differentiated cells. Induction of neural differentiation with retinoic acid resulted in downregulation of Sox2 and VRK1 that inversely correlated with the expression of differentiation markers such as N-cadherin, Pax6, mH2A1.2 and mH2A2. Differentiation-associated macro histones mH2A1.2and mH2A2 inhibit CCND1 and VRK1 expression and also block the activation of the VRK1 promoter by Sox2. VRK1 is a downstream target of Sox2 and both form an autoregulatory loop in epithelial cell differentiation.
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.|Instituto de Investigación Biomédica de Salamanca-IBSAL, Hospital Universitario de Salamanca, 37007 Salamanca, Spain.
authors.forename: David S
authors.initials: DS
authors.lastname: Moura
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors.forename: Isabel F
authors.initials: IF
authors.lastname: Fernández
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Marín-Royo
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: López-Sánchez
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.|Instituto de Investigación Biomédica de Salamanca-IBSAL, Hospital Universitario de Salamanca, 37007 Salamanca, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martín-Doncel
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), CSIC-Universidad de Sevilla-Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, 41013 Sevilla, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Vega
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.|Instituto de Investigación Biomédica de Salamanca-IBSAL, Hospital Universitario de Salamanca, 37007 Salamanca, Spain.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Lazo
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D061986:MCF-7 Cells; D009857:Oncogenes / Q000235:genetics*; D000071841:PAX6 Transcription Factor / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015415:Biomarkers; D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D000071841:PAX6 Transcription Factor; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human