DNA repair · 2020
XPA deficiency affects the ubiquitin-proteasome system function.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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de Sousa Leal Angélica Maria, de Azevedo Medeiros Lázaro Batista, Muñoz-Cadavid Cesar Orlando, de Paula Oliveira Riva, de Souza Timóteo Ana Rafaela, de Oliveira Ana Helena Sales, Luis Fonseca Faustino André, da Silva Vandeclécio Lira, de Souza Sandro José, Braz Petta Lajus Tirzah, de Melo Campos Julliane Tamara Araújo, Agnez-Lima Lucymara Fassarella
Аннотация
Xeroderma 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.