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HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells
HIV-1 infects T cells, but the most frequent AIDS-related lymphomas are of B-cell origin. Molecular mechanisms of HIV-1-induced oncogenic transformation of B cells remain largely unknown. HIV-1 Tat protein may participate in this process by penetrating and regulating gene expression in B cells. Both...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915967/ https://www.ncbi.nlm.nih.gov/pubmed/33557396 http://dx.doi.org/10.3390/ijms22041588 |
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author | Akbay, Burkitkan Germini, Diego Bissenbaev, Amangeldy K. Musinova, Yana R. Sheval, Evgeny V. Vassetzky, Yegor Dokudovskaya, Svetlana |
author_facet | Akbay, Burkitkan Germini, Diego Bissenbaev, Amangeldy K. Musinova, Yana R. Sheval, Evgeny V. Vassetzky, Yegor Dokudovskaya, Svetlana |
author_sort | Akbay, Burkitkan |
collection | PubMed |
description | HIV-1 infects T cells, but the most frequent AIDS-related lymphomas are of B-cell origin. Molecular mechanisms of HIV-1-induced oncogenic transformation of B cells remain largely unknown. HIV-1 Tat protein may participate in this process by penetrating and regulating gene expression in B cells. Both immune and cancer cells can reprogram communications between extracellular signals and intracellular signaling pathways via the Akt/mTORC1 pathway, which plays a key role in the cellular response to various stimuli including viral infection. Here, we investigated the role of HIV-1 Tat on the modulation of the Akt/mTORC1 pathway in B cells. We found that HIV-1 Tat activated the Akt/mTORC1 signaling pathway; this leads to aberrant activation of activation-induced cytidine deaminase (AICDA) due to inhibition of the AICDA transcriptional repressors c-Myb and E2F8. These perturbations may ultimately lead to an increased genomic instability and proliferation that might cause B cell malignancies. |
format | Online Article Text |
id | pubmed-7915967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79159672021-03-01 HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells Akbay, Burkitkan Germini, Diego Bissenbaev, Amangeldy K. Musinova, Yana R. Sheval, Evgeny V. Vassetzky, Yegor Dokudovskaya, Svetlana Int J Mol Sci Article HIV-1 infects T cells, but the most frequent AIDS-related lymphomas are of B-cell origin. Molecular mechanisms of HIV-1-induced oncogenic transformation of B cells remain largely unknown. HIV-1 Tat protein may participate in this process by penetrating and regulating gene expression in B cells. Both immune and cancer cells can reprogram communications between extracellular signals and intracellular signaling pathways via the Akt/mTORC1 pathway, which plays a key role in the cellular response to various stimuli including viral infection. Here, we investigated the role of HIV-1 Tat on the modulation of the Akt/mTORC1 pathway in B cells. We found that HIV-1 Tat activated the Akt/mTORC1 signaling pathway; this leads to aberrant activation of activation-induced cytidine deaminase (AICDA) due to inhibition of the AICDA transcriptional repressors c-Myb and E2F8. These perturbations may ultimately lead to an increased genomic instability and proliferation that might cause B cell malignancies. MDPI 2021-02-04 /pmc/articles/PMC7915967/ /pubmed/33557396 http://dx.doi.org/10.3390/ijms22041588 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Akbay, Burkitkan Germini, Diego Bissenbaev, Amangeldy K. Musinova, Yana R. Sheval, Evgeny V. Vassetzky, Yegor Dokudovskaya, Svetlana HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells |
title | HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells |
title_full | HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells |
title_fullStr | HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells |
title_full_unstemmed | HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells |
title_short | HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells |
title_sort | hiv-1 tat activates akt/mtorc1 pathway and aicda expression by downregulating its transcriptional inhibitors in b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915967/ https://www.ncbi.nlm.nih.gov/pubmed/33557396 http://dx.doi.org/10.3390/ijms22041588 |
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