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PMID:22262847
| Citation |
Agarwal, S, Agarwal, S, Jin, H, Pancholi, P and Pancholi, V (2012) Serine/threonine phosphatase (SP-STP), secreted from Streptococcus pyogenes, is a pro-apoptotic protein. J. Biol. Chem. 287:9147-67 |
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| Abstract |
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. |
| Links |
PubMed PMC3308748 Online version:10.1074/jbc.M111.316554 |
| Keywords |
Animals; Apoptosis; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Cell Line; Humans; Mice; Pharyngeal Diseases/microbiology; Pharyngeal Diseases/physiopathology; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism; Streptococcal Infections/microbiology; Streptococcal Infections/physiopathology; Streptococcus pyogenes/enzymology; Streptococcus pyogenes/genetics; Streptococcus pyogenes/pathogenicity; Virulence |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0052151: positive regulation by symbiont of host apoptotic process |
ECO:0000315: |
P |
Figure 2A STP (Putative phosphoprotein phosphatase) Streptococcus pyogenes “The results from the MTT assays revealed significantly lower inhibition of proliferation of pharyngeal cells treated with GAS strains devoid of SP-STP (M1ΔSTP and M1T1ΔSTP, 5 and 18%, respectively) unlike the wild-type GAS strains (>90% inhibition)... confirm[ing] that SP-STP plays a significant role in GAS-mediated apoptosis (Fig. 2A).” |
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Notes
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References
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