HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells.
Int J Mol Sci
; 22(4)2021 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-33557396
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Linfócitos B
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Regulação da Expressão Gênica
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Citidina Desaminase
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Proteínas Proto-Oncogênicas c-akt
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Produtos do Gene tat do Vírus da Imunodeficiência Humana
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Alvo Mecanístico do Complexo 1 de Rapamicina
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article