XPA deficiency affects the ubiquitin-proteasome system function.

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. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Angélica Maria de Sousa Leal, Lázaro Batista de Azevedo Medeiros, Cesar Orlando Muñoz-Cadavid, Riva de Paula Oliveira, Ana Rafaela de Souza Timóteo, Ana Helena Sales de Oliveira, André Luis Fonseca Faustino, Vandeclécio Lira da Silva, Sandro José de Souza, Tirzah Braz Petta Lajus, Julliane Tamara Araújo de Melo Campos, Lucymara Fassarella Agnez-Lima. XPA deficiency affects the ubiquitin-proteasome system function. DNA repair. 2020 Oct;94:102937

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PMID: 32693352

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