Serine/threonine phosphatase (SP-STP), secreted from streptococcus pyogenes, is a pro-apoptotic protein

Shivani Agarwal, Shivangi Agarwal, Hong Jin, Preeti Pancholi, Vijay Pancholi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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 wildtype 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.

Original languageEnglish (US)
Pages (from-to)9147-9167
Number of pages21
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Mar 16 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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