Document Detail


Cell cycle regulation of the double stranded RNA activated protein kinase, PKR.
MedLine Citation:
PMID:  9927188     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The interferon (IFN)-induced, double stranded RNA (dsRNA)-activated serine/threonine kinase, PKR, is a potent negative regulator of cell growth when overexpressed in yeast or mammalian cells. To determine whether endogenous PKR plays a role in cell growth control, we have investigated the regulation of PKR levels and activity during the cell cycle in human glioblastoma T98G cells. The steady-state level of PKR mRNA in T98G cells was highest in growth arrested cells, dropped sharply within 3 h of serum stimulation then gradually increased as cells progressed through G1, reaching a plateau in early S phase. PKR protein level increased following serum stimulation reaching a peak at the G2+M boundary and declining thereafter. In contrast, PKR kinase activity exhibited two peaks, in early G1 and at the G1/S boundary, declining sharply in early S phase. Thus, the activity profile did not follow the protein profile indicating a tight regulation of PKR at the level of activity. In T98G cells expressing the catalytically inactive PKRK296R the dsRNA-induced activation of NF-kappaB and IRF-1 was suppressed and the mutant cells exhibited resistance to stress induced apoptosis. Cell cycle distribution analysis showed that the mutant expressing cells exhibited longer G1 phase and fewer cells engaged in S phase. Furthermore, early passage mouse embryo fibroblasts derived from PKR knockout mice grew more slowly compared with the control cells. Taken together these results suggest that PKR may play a role in cell cycle progression.
Authors:
M Zamanian-Daryoush; S D Der; B R Williams
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  18     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-16     Completed Date:  1999-02-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  315-26     Citation Subset:  IM    
Affiliation:
Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Cell Cycle*
Cell Cycle Proteins / genetics,  metabolism*
Cell Division
DNA Primers
Humans
Mice
NF-kappa B / metabolism
RNA, Double-Stranded / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
eIF-2 Kinase / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
AI34039/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA Primers; 0/NF-kappa B; 0/RNA, Double-Stranded; EC 2.7.11.1/eIF-2 Kinase

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