HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells

Autor: Yegor S. Vassetzky, Evgeny V. Sheval, Amangeldy K. Bissenbaev, Burkitkan Akbay, Svetlana Dokudovskaya, Diego Germini, Yana R. Musinova
Přispěvatelé: CNRS UMR9018, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France, Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Al-Farabi Kazakh National University [Almaty] (KazNU), Koltzov Institute of Developmental Biology, the Russian Academy of Sciences [Moscow, Russia] (RAS), Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University (MSU), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2020
Předmět:
[SDV]Life Sciences [q-bio]
mTORC1
AICDA
lcsh:Chemistry
0302 clinical medicine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Gene expression
Activation-induced (cytidine) deaminase
lcsh:QH301-705.5
Spectroscopy
Cells
Cultured
0303 health sciences
B-Lymphocytes
biology
General Medicine
Cytidine deaminase
3. Good health
Computer Science Applications
Cell biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
tat Gene Products
Human Immunodeficiency Virus
Transcriptional Activation
[SDV.CAN]Life Sciences [q-bio]/Cancer
Mechanistic Target of Rapamycin Complex 1
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Proto-Oncogene Proteins c-myb
Immune system
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Cytidine Deaminase
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Protein kinase B
B cell
030304 developmental biology
Akt/mTORC1 pathway
B cells
Organic Chemistry
Repressor Proteins
lcsh:Biology (General)
lcsh:QD1-999
Gene Expression Regulation
Cancer cell
biology.protein
HIV-1
Tat
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
DNA Damage
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, MDPI, 2021, 22 (4), pp.1588. ⟨10.3390/ijms22041588⟩
International Journal of Molecular Sciences, Vol 22, Iss 1588, p 1588 (2021)
Volume 22
Issue 4
ISSN: 1422-0067
1661-6596
Popis: 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.
Databáze: OpenAIRE
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