title: Protein glutathionylation in the regulation of peroxiredoxins: a family of thiol-specific peroxidases that function as antioxidants, molecular chaperones, and signal modulators.
abstract: CONCLUSIONS
  Reversible protein glutathionylation plays an important role in cellular regulation, signaling transduction, and antioxidant defense. This redox-sensitive mechanism is involved in regulating the functions of peroxiredoxins (Prxs), a family of ubiquitously expressed thiol-specific peroxidase enzymes. Glutathionylation of certain Prxs at their active-site cysteines not only provides reducing equivalents to support their peroxidase activity but also protects Prxs from irreversible hyperoxidation. Typical 2-Cys Prx also functions as a molecular chaperone when it exists as a decamer and/or higher molecular weight complexes. The hyperoxidized sulfinic derivative of 2-Cys Prx is reactivated by sulfiredoxin (Srx). In this review, the roles of glutathionylation in the regulation of Prxs are discussed with respect to their molecular structure and functions as antioxidants, molecular chaperones, and signal modulators.
  
  
  BACKGROUND
  Recent findings reveal that glutathionylation regulates the quaternary structure of Prx. Glutathionylation of Prx I at Cys(83) converts the decameric Prx to its dimers with the loss of chaperone activity. The findings that dimer/oligomer structure specific Prx I binding proteins, e.g., phosphatase and tensin homolog (PTEN) and mammalian Ste20-like kinase-1 (MST1), regulate cell cycle and apoptosis, respectively, suggest a possible link between glutathionylation and those signaling pathways.
  
  
  RESULTS
  Knowing how glutathionylation affects the interaction between Prx I and its nearly 20 known interacting proteins, e.g., PTEN and MST1 kinase, would reveal new insights on the physiological functions of Prx.
  
  
  CONCLUSIONS
  In vitro studies reveal that Prx oligomerization is linked to its functional changes. However, in vivo dynamics, including the effect by glutathionylation, and its physiological significance remain to be investigated.
authors: School of Biological Sciences and Technology, Chonnam National University, Gwangju, Korea.
authors: Ho Zoon
authors: HZ
authors: Chae
authors: Hammou
authors: H
authors: Oubrahim
authors: Ji Won
authors: JW
authors: Park
authors: Sue Goo
authors: SG
authors: Rhee
authors: P Boon
authors: PB
authors: Chock
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D018832:Molecular Chaperones; D054464:Peroxiredoxins; D005978:Glutathione