Akt Pathway Activation by Human T-cell Leukemia Virus Type 1 Tax Oncoprotein |
| |
Authors: | Mathew A Cherian Hicham H Baydoun Jacob Al-Saleem Nikoloz Shkriabai Mamuka Kvaratskhelia Patrick Green Lee Ratner |
| |
Institution: | From the ‡Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 and ;the §Center for Retrovirus Research and ;Departments of ‖Pharmaceutics and Pharmaceutical Chemistry and ;¶Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210 |
| |
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. |
| |
Keywords: | Akt PKB PDZ domain phosphatase and tensin homolog (PTEN) protein serine/threonine phosphatase (PSP) retrovirus |
|
|