Document Detail


Deregulation of poly(A) polymerase interferes with cell growth.
MedLine Citation:
PMID:  9710585     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vertebrate poly(A) polymerase (PAP) contains a catalytic domain and a C-terminal Ser-Thr-rich regulatory region. Consensus and nonconsensus cyclin-dependent kinase (cdk) sites are conserved in the Ser-Thr-rich region in vertebrate PAPs. PAP is phosphorylated by cdc2-cyclin B on these sites in vitro and in vivo and is inactivated by hyperphosphorylation in M-phase cells, when cdc2-cyclin B is active. In the experiments described here, we undertook a genetic approach in chicken DT40 cells to study the function of PAP phosphorylation. We found that PAP is highly conserved in chicken and is essential in DT40 cells. While cells could tolerate reduced levels of PAP, even modest overexpression of either wild-type PAP or a mutant PAP with two consensus cdk sites mutated (cdk- PAP) was highly deleterious and at a minimum resulted in reduced growth rates. Importantly, cells that expressed cdk- PAP had a significantly lower growth rate than did cells that expressed similar levels of wild-type PAP, which was reflected in increased accumulation of cells in the G0-G1 phase of the cell cycle. We propose that the lower growth rate is due to the failure of hyperphosphorylation and thus M-phase inactivation of cdk- PAP.
Authors:
W Zhao; J L Manley
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  18     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-09-10     Completed Date:  1998-09-10     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5010-20     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Binding Sites
CDC2 Protein Kinase / metabolism
Cattle
Cell Division
Cell Line
Chickens
Conserved Sequence
Cyclin B / metabolism
Cyclin-Dependent Kinase 5
Cyclin-Dependent Kinases*
Exons
Heterozygote
Humans
Kinetics
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Phosphorylation
Polynucleotide Adenylyltransferase / biosynthesis*,  chemistry*,  genetics
Protein-Serine-Threonine Kinases / metabolism
Ranidae
Recombinant Proteins / biosynthesis,  chemistry,  metabolism
Sequence Alignment
Transfection
Vertebrates
Grant Support
ID/Acronym/Agency:
GM 28983/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin B; 0/Recombinant Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2 Protein Kinase; EC 2.7.11.22/CDK5 protein, human; EC 2.7.11.22/Cdk5 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 5; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.7.19/Polynucleotide Adenylyltransferase
Comments/Corrections

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