PKM2-mediated inhibition of autophagy facilitates Tat's inducing HIV-1 transactivation.
Arch Biochem Biophys
; 625-626: 17-23, 2017 07 01.
Article
em En
| MEDLINE
| ID: mdl-28583828
ABSTRACT
Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression. In addition, we showed that PI3K/AKT activation and AMPK inhibtion was required for the PKM2-mediated inhibition of autophagy in Tat-treated TZM-bl cells. In conclusion, our data reveals that PKM2-mediated autophagy inhibition is required for Tat-mediated HIV-1 transactivation. Metabolism-related autophagic pathway may act as a promising diagnostic and therapeutic tool for HIV-1 infection in the future.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Hormônios Tireóideos
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Proteínas de Transporte
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Infecções por HIV
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Ativação Transcricional
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HIV-1
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Produtos do Gene tat do Vírus da Imunodeficiência Humana
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article