title: FBXO25 regulates MAPK signaling pathway through inhibition of ERK1/2 phosphorylation.
abstract: The FBXO25 mediates degradation of ELK-1 and thus inhibits transcriptional activation of immediate early genes (iEG). Here we show that FBXO25 regulates yet another node of this signaling pathway, by decreasing MAPK/ERK activity. We show that induction of FBXO25 reduced ERK1/2 phosphorylation independently of MEK1/2. Accordingly, in HAP1 FBXO25 knockout cells (FBXO25KO), we observed that upon PMA treatment ERK1/2 was more active than in parental cells. An increase in cell proliferation under receptor mediated activation of the ERK signaling pathway in FBXO25KOcells was also observed. Taken together we show that FBXO25 functions as a negative regulator of MAPK signaling though the reduction of ERK1/2 activation.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil; Department of Genetics and Evolution, Federal University of Sao Carlos, Brazil.
authors.forename: Felipe R
authors.initials: FR
authors.lastname: Teixeira
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil.
authors.forename: Adriana O
authors.initials: AO
authors.lastname: Manfiolli
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil.
authors.forename: Nichelle A
authors.initials: NA
authors.lastname: Vieira
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil.
authors.forename: Ana Carla
authors.initials: AC
authors.lastname: Medeiros
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil.
authors.forename: Priscila de O
authors.initials: PO
authors.lastname: Coelho
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil.
authors.forename: Dimitrius
authors.initials: D
authors.lastname: Santiago Guimarães
authors.affiliation: Department of Biochemistry, Chemistry Institute, University of São Paulo, Brazil.
authors.forename: Deborah
authors.initials: D
authors.lastname: Schechtman
authors.affiliation: Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil. Electronic address: mdamario@fmrp.usp.br.
authors.forename: Marcelo D
authors.initials: MD
authors.lastname: Gomes
mesh_terms: D044783:F-Box Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D044783:F-Box Proteins; C510759:FBXO25 protein, human; D009419:Nerve Tissue Proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ELK-1; ERK1/2; FBXO25; MEK1/2