Hepatitis C virus–induced up-regulation of protein phosphatase 2A inhibits histone modification and DNA damage repair

Hepatology ◽  
2009 ◽  
pp. NA-NA ◽  
Author(s):  
Francois H. T. Duong ◽  
Verena Christen ◽  
Shanshan Lin ◽  
Markus H. Heim
Keyword(s):  
Dna Damage ◽  
Hepatitis C ◽  
Histone Modification ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Phosphatase 2A

The protein phosphatase 2A represents a novel cellular target for hepatitis C virus NS5A protein

Biochimie ◽  
2006 ◽  
Vol 88 (6) ◽  
pp. 651-662 ◽  
Author(s):  
Urania Georgopoulou ◽  
Panagiota Tsitoura ◽  
Maria Kalamvoki ◽  
Penelope Mavromara
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Ns5a Protein ◽  
Cellular Target ◽  
Phosphatase 2A

scholarly journals Protein Phosphatase 2A Antagonizes ATM and ATR in a Cdk2- and Cdc7-Independent DNA Damage Checkpoint

2006 ◽  
Vol 26 (5) ◽  
pp. 1997-2011 ◽  
Author(s):  
Paris Petersen ◽  
Danny M. Chou ◽  
Zhongsheng You ◽  
Tony Hunter ◽  
Johannes C. Walter ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Protein Phosphatase ◽  
Ataxia Telangiectasia ◽  
Protein Phosphatase 2A ◽  
Inhibitory Effect ◽  
Dna Damage Checkpoint ◽  
Free System ◽  
Phosphatase 2A ◽  
Initiation Of Dna Replication

ABSTRACT We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. We found that immunodepletion of PP2A or inhibition of PP2A by okadaic acid (OA) inhibits initiation of DNA replication by preventing loading of the initiation factor Cdc45 onto prereplication complexes. Evidence was provided that PP2A counteracts an inhibitory protein kinase that phosphorylates and inactivates a crucial Cdc45 loading factor. Here, we report that the inhibitory effect of OA is abolished by caffeine, an inhibitor of the checkpoint kinases ataxia-telangiectasia mutated protein (ATM) and ataxia-telangiectasia related protein (ATR) but not by depletion of ATM or ATR from the extract. Furthermore, we demonstrate that double-strand DNA breaks (DSBs) cause inhibition of Cdc45 loading and initiation of DNA replication and that caffeine, as well as immunodepletion of either ATM or ATR, abolishes this inhibition. Importantly, the DSB-induced inhibition of Cdc45 loading is prevented by addition of the catalytic subunit of PP2A to the extract. These data suggest that DSBs and OA prevent Cdc45 loading through different pathways, both of which involve PP2A, but only the DSB-induced checkpoint implicates ATM and ATR. The inhibitory effect of DSBs on Cdc45 loading does not result from downregulation of cyclin-dependent kinase 2 (Cdk2) or Cdc7 activity and is independent of Chk2. However, it is partially dependent on Chk1, which becomes phosphorylated in response to DSBs. These data suggest that PP2A counteracts ATM and ATR in a DNA damage checkpoint in Xenopus egg extracts.

Virus-induced over-expression of protein phosphatase 2A inhibits insulin signalling in chronic hepatitis C

2008 ◽  
Vol 49 (3) ◽  
pp. 429-440 ◽  
Author(s):  
Christine Bernsmeier ◽  
Francois H.T. Duong ◽  
Verena Christen ◽  
Paolo Pugnale ◽  
Francesco Negro ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Protein Phosphatase ◽  
Insulin Signalling ◽  
Protein Phosphatase 2A ◽  
Over Expression ◽  
Phosphatase 2A
Sign in / Sign up

Export Citation Format

Share Document