Akt Pathway Activation by Human T-cell Leukemia Virus Type 1 Tax Oncoprotein.

The Journal of Biological Chemistry
Mathew A CherianLee Ratner

Abstract

Human T-cell leukemia virus (HTLV) type 1, the etiological agent of adult T-cell leukemia, expresses the viral oncoprotein Tax1. In contrast, HTLV-2, which expresses Tax2, is non-leukemogenic. One difference between these homologous proteins is the presence of a C-terminal PDZ domain-binding motif (PBM) in Tax1, previously reported to be important for non-canonical NFκB activation. In contrast, this study finds no defect in non-canonical NFκB activity by deletion of the Tax1 PBM. Instead, Tax1 PBM was found to be important for Akt activation. Tax1 attenuates the effects of negative regulators of the PI3K-Akt-mammalian target of rapamycin pathway, phosphatase and tensin homologue (PTEN), and PHLPP. Tax1 competes with PTEN for binding to DLG-1, unlike a PBM deletion mutant of Tax1. Forced membrane expression of PTEN or PHLPP overcame the effects of Tax1, as measured by levels of Akt phosphorylation, and rates of Akt dephosphorylation. The current findings suggest that Akt activation may explain the differences in transforming activity of HTLV-1 and -2.

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Citations

Jan 23, 2016·Pathogens·Claire D James, Sally Roberts
Nov 18, 2017·Annual Review of Immunology·Charles R M Bangham
Mar 16, 2018·The Journal of Biological Chemistry·Mathew A CherianDaniel Rauch
Jul 25, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luis H Gutiérrez-González, Teresa Santos-Mendoza
Mar 23, 2018·PLoS Pathogens·Eléonore PérèsMadeleine Duc Dodon
Apr 22, 2020·Advanced Therapeutics·Nikolaj R ChristensenKristian Strømgaard
Jan 21, 2016·Proteomes·Haitham Sobhy
Jun 15, 2018·International Journal of Oncology·Chie IshikawaNaoki Mori
Aug 9, 2019·Retrovirology·Michael P MartinezPatrick L Green
Sep 4, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Caroline KelloggIgor F Tsigelny

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