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Protein phosphatase 2A inhibits interferon signaling through the Jak STAT pathway and promotes hepatitis C viral replication

Shanker, Vijay. Protein phosphatase 2A inhibits interferon signaling through the Jak STAT pathway and promotes hepatitis C viral replication. 2014, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_10966

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Abstract

The first part of the work demonstrate the role of PP2A in IFN-α induced Jak-STAT1 signaling and HCV replication. We show here that PP2Ac activity is not required for IFN-α induced tyrosine phosphorylation of Jak1/Tyk2 and STAT1. In response to IFN-α induction, PP2Ac associates with Jak1/Tyk2 and STAT1. This association modulates the Jak1/Tyk2 and STAT1 tyrosine phosphorylation. However, this study shows that PP2A activity is required for the HCV replication.
The selective behavior of PP2A for Jak-STAT1 signaling pathway inhibition and promotion of HCV replication could be due to the targeted substrate selection by PP2A holoenzyme complex. In the second part of this work, attempts were made to determine the specific regulatory B subunits involved in IFN-α induced Jak-STAT1 signaling inhibition and HCV replication. We observed the inter-regulatory behavior of PP2A subunits. During the course of this study, due to unavailability of specific antibodies for various isoforms of B subunit, the aim to determine specific holoenzyme complex involved in regulation of Jak-STAT1 signaling and HCV replication was not achieved.
Further studies are required to investigate the specific B subunits and thereby holoenzyme complex responsible for IFN-α induced Jak-STAT signaling inhibition and HCV replication by PP2A.
Advisors:Heim, Markus Hermann
Committee Members:Wymann, Matthias Paul
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
Item Type:Thesis
Thesis no:10966
Bibsysno:Link to catalogue
Number of Pages:91 p.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:56
Deposited On:03 Nov 2014 12:43

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