Protein Synthesis Regulation by Sumoylation

• Grant number: 11/21350-4
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2012
• Effective date (End): February 28, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Vilma Regina Martins
• Grantee: Martín Roffé
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches, AP.TEM

Abstract

Sumoylation is a post-translational modification that alters the function and/or localization of target proteins. In general, the sumoylation pathway has been associated to the control of nuclear phenomena, such as transcriptional regulation. However, in the last years, increasing evidence of extra-nuclear functions emerged for this pathway. Among these new functions, only two publications pointed to sumoylation as a new regulator of mRNA translation in mammalian cells. In those works, the effects of eukaryotic translation initiation factor 4E (eIF4E) sumoylation were studied. Furthermore, in a proteomic study in Drosophila melanogaster, several ribosomal proteins and factors associated with the translational control were found to be targets for sumoylation. In this manner, sumoylation might be another mechanism of translational control not explored yet in mammalian cells. The objective of this project is the identification of proteins involved in the control of translation in mammalian cells that are targets for sumoylation. For that purpose, we shall perform high-throughput analysis of sumoylated proteins that associate with polysomes, followed by the confirmation of the hits and the analysis of how sumoylation affects the function of the corresponding proteins. Translational deregulation is a common phenomenon for several tumor types. Preliminary results from our laboratory show alterations in several components of the sumoylation pathway in glioblastomas. For that reason, we will study if the sumoylation pathway is responsible, or a contributor, for the translational deregulation observed in glioblastomas, together with the identification of the affected factors.

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)

ROFFE, MARTIN; LUPINACCI, FERNANCLA C.; SOARES, LUANA C.; HAJJ, GLAUCIA N.; MARTINS, VILMA R.. Two widely used RSK inhibitors, BI-D1870 and SL0101, alter mTORC1 signaling in a RSK-independent manner. CELLULAR SIGNALLING, v. 27, n. 8, p. 1630-1642, AUG 2015. (13/25025-6, 11/21350-4, 13/03315-2, 09/14027-2, 12/04370-4)