Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1

Alessandra Spaziani, Anna Alisi, Donatella Sanna, Clara Balsano

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Some hepatitis C virus (HCV) proteins, including core protein, deregulate the cell cycle of infected cells, thereby playing an important role in the viral pathogenesis of HCC. Thus far, there are only few studies that have deeply investigated in depth the effects of the HCV core protein expression on the progression through the G1/S and G2/M phases of the cell cycle. To shed light on the molecular mechanisms by which the HCV core protein modulates cell proliferation, we have examined its effects on cell cycle in hepatocarcinoma cells. We show here that HCV core protein perturbs progression through both the G1/S and the G2/M phases, by modulating the expression and the activity of several cell cycle regulatory proteins. In particular, our data provided evidence that core-dependent deregulation of the G1/S phase and its related cyclin-CDK complexes depends upon the ERK1/2 pathway. On the other hand, the viral protein also increases the activity of the cyclin B1-CDK1 complex via the p38 MAPK and JNK pathways. Moreover, we show that HCV core protein promotes nuclear import of cyclin B1, which is affected by the inhibition of both the p38 and the RNA-dependent protein kinase (PKR) activities. The important role of p38 MAPK in regulating G2/M phase transition has been previously documented. It is becoming clear that PKR has an important role in regulating both the G1/S and the G 2/M phase, in which it induces M phase arrest. Based on our model, we now show, for the first time, that HCV core expression leads to deregulation of the mitotic checkpoint via a p38/PKR-dependent pathway.

Original languageEnglish
Pages (from-to)10983-10989
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number16
DOIs
Publication statusPublished - Apr 21 2006

Fingerprint

eIF-2 Kinase
Cyclin B1
p38 Mitogen-Activated Protein Kinases
Viruses
Hepacivirus
Cell Division
G2 Phase
Cell Cycle Proteins
Deregulation
MAP Kinase Signaling System
Cells
Cell Cycle
Cyclins
M Phase Cell Cycle Checkpoints
Cell proliferation
Viral Proteins
Cell Nucleus Active Transport
Phase Transition
G1 Phase
S Phase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1. / Spaziani, Alessandra; Alisi, Anna; Sanna, Donatella; Balsano, Clara.

In: Journal of Biological Chemistry, Vol. 281, No. 16, 21.04.2006, p. 10983-10989.

Research output: Contribution to journalArticle

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