Document Detail


Serine/threonine phosphatase (SP-STP), secreted from Streptococcus pyogenes, is a pro-apoptotic protein.
MedLine Citation:
PMID:  22262847     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This investigation illustrates an important property of eukaryote-type serine/threonine phosphatase (SP-STP) of group A Streptococcus (GAS) in causing programmed cell death of human pharyngeal cells. The secretory nature of SP-STP, its elevated expression in the intracellular GAS, and the ability of wild-type GAS but not the GAS mutant devoid of SP-STP to cause apoptosis of the host cell both in vitro and in vivo suggest that GAS deploys SP-STP as an important virulence determinant to exploit host cell machinery for its own advantage during infection. The exogenously added SP-STP is able to enter the cytoplasm and subsequently traverses into the nucleus in a temporal fashion to cause apoptosis of the pharyngeal cells. The programmed cell death induced by SP-STP, which requires active transcription and de novo protein synthesis, is also caspase-dependent. Furthermore, the entry of SP-STP into the cytoplasm is dependent on its secondary structure as the catalytically inactive SP-STP with an altered structure is unable to internalize and cause apoptosis. The ectopically expressed wild-type SP-STP was found to be in the nucleus and conferred apoptosis of Detroit 562 pharyngeal cells. However, the catalytically inactive SP-STP was unable to cause apoptosis even when intracellularly expressed. The ability of SP-STP to activate pro-apoptotic signaling cascades both in the cytoplasm and in the nucleus resulted in mitochondrial dysfunctioning and perturbation in the phosphorylation status of histones in the nucleus. SP-STP thus not only functions as a virulence regulator but also as an important factor responsible for host-related pathogenesis.
Authors:
Shivani Agarwal; Shivangi Agarwal; Hong Jin; Preeti Pancholi; Vijay Pancholi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-19
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-06-12     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9147-67     Citation Subset:  IM    
Affiliation:
Department of Pathology, Ohio State University College of Medicine, Columbus, Ohio 43210-1214, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Apoptosis Regulatory Proteins / genetics,  metabolism*
Bacterial Proteins / genetics,  metabolism*
Cell Line
Humans
Mice
Pharyngeal Diseases / microbiology,  physiopathology
Phosphoprotein Phosphatases / genetics,  metabolism*
Streptococcal Infections / microbiology*,  physiopathology*
Streptococcus pyogenes / enzymology*,  genetics,  pathogenicity
Virulence
Grant Support
ID/Acronym/Agency:
AI64912/AI/NIAID NIH HHS; AI76889/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bacterial Proteins; EC 3.1.3.16/Phosphoprotein Phosphatases
Comments/Corrections

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