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

Author(s)

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

• Document type: Journal article
• Source: Archives of Biochemistry and Biophysics; v. 621, p. 38-45, MAY 1 2017.
• Web of Science Citations: 2

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. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 14/10898-7 - High-throughput RNAi library screening to identify novel regulators of ERKs
• Grantee: Marcelo Damário Gomes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/16464-8 - Application of protein microarray to identify substrates of SCF1 (FBXO25) E3 ubiquitin ligase
• Grantee: Felipe Roberti Teixeira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/21891-5 - PRODUCTION AND FUNCTIONAL ANALYSIS OF HUMAN NEURONAL CELLS GENETICALLY MODIFIED TO REGULATE THE UBIQUITIN LIGASE FBXO25 EXPRESSION
• Grantee: Adriana Oliveira Manfiolli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral