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Activation of endoplasmic reticulum stress response by hepatitis viruses up‐regulates protein phosphatase 2A
Author(s) -
Christen Verena,
Treves Susan,
Duong Francois H. T.,
Heim Markus H.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21611
Subject(s) - creb , protein phosphatase 2 , endoplasmic reticulum , microbiology and biotechnology , unfolded protein response , signal transduction , phosphatase , protein kinase a , biology , protein phosphatase 1 , phosphorylation , chemistry , transcription factor , biochemistry , gene
The up‐regulation of protein phosphatase 2 A (PP2A) is an important factor leading to an inhibition of IFNα signaling caused by viral protein expression. Here, we describe the molecular mechanism involved in PP2Ac up‐regulation by HCV and HBV. HCV and HBV protein expression in cells induces an ER stress response leading to calcium release from the ER. HCV protein expression induces CREB activation, probably through calcium/calmodulin‐dependent protein kinase. CREB binds to a CRE element in the promoter of PP2Ac and induces its transcriptional up‐regulation. Because PP2Ac is involved in many important cellular processes including cell‐cycle regulation, apoptosis, cell morphology, development, signal transduction and translation, its up‐regulation during ER stress has potentially important implications. (H EPATOLOGY 2007.)