Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Chemogenomic Study of Carboplatin in Saccharomyces cerevisiae: Inhibition of the NEDDylation Process Overcomes Cellular Resistance Mediated by HuR and Cullin Proteins

Full text
Author(s):
de Sousa, Graziele Fonseca [1] ; Lima, Maira de Assis [2] ; Custodio, Debora Fernandes [1] ; Freitas, Vanessa Morais [2] ; Monteiro, Gisele [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Tecnol Bioquim Farmaceut, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular Desenvolvimento, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: PLoS One; v. 10, n. 12 DEC 21 2015.
Web of Science Citations: 9
Abstract

The use of carboplatin in cancer chemotherapy is limited by the emergence of drug resistance. To understand the molecular basis for this resistance, a chemogenomic screen was performed in 53 yeast mutants that had previously presented strong sensitivity to this widely used anticancer agent. Thirty-four mutants were responsive to carboplatin, and from these, 21 genes were selected for further studies because they have human homologues. Sixty percent of these yeast genes possessed human homologues which encoded proteins that interact with cullin scaffolds of ubiquitin ligases, or whose mRNA are under the regulation of Human antigen R (HuR) protein. Both HuR and cullin proteins are regulated through NED-Dylation post-translational modification, and so our results indicate that inhibition of this process should sensitise resistant tumour cells to carboplatin. We showed that treatment of a tumour cell line with MLN4924, a NEDDylation inhibitor, overcame the resistance to carboplatin. Our data suggest that inhibition of NEDDylation may be a useful strategy to resensitise tumour cells in patients that have acquired carboplatin resistance. (AU)

FAPESP's process: 11/04173-1 - Identification of molecular targets asscociated with resistance to antitumor drugs Carboplatin and Rebeccamycin analogues using Saccharomyces cerevisiae as model cell
Grantee:Graziele Fonseca de Sousa
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 09/01303-1 - Characterization of unknown function ORFs involved in Saccharomyces cerevisiae antioxidant response
Grantee:Gisele Monteiro
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 15/07749-2 - Protein engineering and comparison of microbial expression systems of the biopharmaceutical L-asparaginase
Grantee:Gisele Monteiro
Support Opportunities: Regular Research Grants