FBXO25 regulates MAPK signaling pathway through inhibition of ERK1/2 phosphorylation

Felipe R Teixeira; Adriana O Manfiolli; Nichelle A Vieira; Ana Carla Medeiros; Priscila de O Coelho; Dimitrius Santiago Guimarães; Deborah Schechtman; Marcelo D Gomes

doi:10.1016/j.abb.2017.04.003

FBXO25 regulates MAPK signaling pathway through inhibition of ERK1/2 phosphorylation

Arch Biochem Biophys. 2017 May 1:621:38-45. doi: 10.1016/j.abb.2017.04.003. Epub 2017 Apr 5.

Authors

Felipe R Teixeira¹, Adriana O Manfiolli², Nichelle A Vieira², Ana Carla Medeiros², Priscila de O Coelho², Dimitrius Santiago Guimarães², Deborah Schechtman³, Marcelo D Gomes⁴

Affiliations

¹ 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.
² Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil.
³ Department of Biochemistry, Chemistry Institute, University of São Paulo, Brazil.
⁴ Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Brazil. Electronic address: mdamario@fmrp.usp.br.

PMID: 28389297
DOI: 10.1016/j.abb.2017.04.003

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 (FBXO25^KO), 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 FBXO25^KO cells was also observed. Taken together we show that FBXO25 functions as a negative regulator of MAPK signaling though the reduction of ERK1/2 activation.

Keywords: ELK-1; ERK1/2; FBXO25; MEK1/2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

F-Box Proteins / metabolism*
Gene Expression Regulation, Enzymologic / physiology*
HEK293 Cells
Humans
MAP Kinase Signaling System / physiology*
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Nerve Tissue Proteins / metabolism*
Phosphorylation

Substances

F-Box Proteins
FBXO25 protein, human
Nerve Tissue Proteins
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3