Navegando por Autor "Faustino, André Luis Fonseca"
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Artigo XPA deficiency affects the ubiquitin-proteasome system function(Elsevier, 2020-07) Leal, Angélica Maria de Sousa; Medeiros, Lázaro Batista de Azevedo; Muñoz-Cadavid, Cesar Orlando; Oliveira, Riva de Paula; Timóteo, Ana Rafaela de Souza; Oliveira, Ana Helena Sales de; Faustino, André Luis Fonseca; Silva, Vandeclécio Lira da; Souza, Sandro José de; Lajus, Tirzah Braz Petta; Campos, Julliane Tamara Araújo de Melo; Agnez-Lima, Lucymara FassarellaXeroderma pigmentosum complementation group A (XPA), is defective in xeroderma pigmentosum patients, causing pre-disposition to skin cancer and neurological abnormalities, which is not well understood. Here, we analyzed the XPA-deficient cells transcriptional profile under oxidative stress. The imbalance in of ubiquitin-proteasome system (UPS) gene expression was observed in XPA-deficient cells and the involvement of nuclear factor erythroid 2-related factor-2 (NFE2L2) was indicated. Co-immunoprecipitation assays showed the interaction between XPA, apurinic-apyrimidinic endonuclease 1 (APE1) and NFE2L2 proteins. Decreased NFE2L2 protein expression and proteasome activity was also observed in XPA-deficient cells. The data suggest the involvement of the growth arrest and DNA-damage-inducible beta (GADD45β) in NFE2L2 functions. Similar results were obtained in xpa-1 (RNAi) Caenorhabditis elegans suggesting the conservation of XPA and NFE2L2 interactions. In conclusion, stress response activation occurs in XPA-deficient cells under oxidative stress; however, these cells fail to activate the UPS cytoprotective response, which may contribute to XPA patient’s phenotypes.