Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 625, Issue -, Pages 17-23Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2017.05.018
Keywords
Tat; Autophagy; PKM2; AMPK
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Funding
- practical training plan for the cross training of high level talents in Beijing Universities [2017070, 2017075]
- Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions [CITTCD201304054]
- National Natural Sciences Foundation of China [30800580]
- Beijing Nova Program [2007B014]
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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. (C) 2017 Elsevier Inc. All rights reserved.
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