High-throughput RNAi library screening to identify novel regulators of ERKs

• Grant number: 14/10898-7
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2014
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcelo Damário Gomes
• Grantee: Marcelo Damário Gomes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The dephosphorylation of ERK1/2 is a critical process in regulating the duration of MAPK signaling activation. Recently, we show that FBXO25 interacts, mediates ubiquitination and proteasomal degradation of ELK-1 protooncogene regulator. FBXO25 inhibits the activation of two ELK-1 target genes, c-fos and egr-1, in response to PMA. Downstream ELK-1, FBXO25 mediates the dephosphorylating of ERK1/2. In addition to regulation by phosphorylation and dephosphorylation MAPKKK1 (MEKK1), which has a RING finger-like structure, exhibits E3 Ub ligase activity toward ERK1/2. Apparently different mechanisms exist to inhibiting ERK1/2 activation: dephosphorylation (transient) without a decrease in ERK1/2 protein levels and ubiquitination-mediated degradation (permanent) of ERK1/2 without dephosphorylation. Based on that, i propose here RNAi library screenings to identify new regulators of ERKs. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TEIXEIRA, FELIPE R.; MANFIOLLI, ADRIANA O.; VIEIRA, NICHELLE A.; MEDEIROS, ANA CARLA; COELHO, PRISCILA DE O.; GUIMARAES, DIMITRIUS SANTIAGO; SCHECHTMAN, DEBORAH; GOMES, MARCELO D.. FBXO25 regulates MAPK signaling pathway through inhibition of ERK1/2 phosphorylation. Archives of Biochemistry and Biophysics, v. 621, p. 38-45, MAY 1 2017. (14/10898-7, 10/16464-8, 11/21891-5)

COELHO, PRISCILA DE O.; GUARNIER, FLAVIA A.; FIGUEIREDO, LEONARDO BRUNO; ZARAMELA, LIVIA S.; PACINI, ENIO S. A.; GODINHO, ROSELY O.; GOMES, MARCELO D.. Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy. Archives of Biochemistry and Biophysics, v. 663, p. 173-182, MAR 15 2019. (15/07019-4, 14/10898-7, 11/07487-7)

MEDEIROS, ANA CARLA; SOARES, CLAUDIA S.; COELHO, PRISCILA O.; VIEIRA, NICHELLE A.; BAQUI, MUNIRA M. A.; TEIXEIRA, FELIPE R.; GOMES, MARCELO D.. DNA damage response signaling does not trigger redistribution of SAMHD1 to nuclear foci. Biochemical and Biophysical Research Communications, v. 499, n. 4, p. 790-796, MAY 23 2018. (14/10898-7, 10/19435-9, 16/00792-2)