S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function. (13th May 2012)

• Record Type: Journal Article
• Authors: Xiong, Ying; Manevich, Yefim; Tew, Kenneth D.; Townsend, Danyelle M.
• Other Names: Filomeni Giuseppe Academic Editor.
• Is Part Of: International journal of cell biology. Volume 2012(2012)
• Publication Date: 2012-05-13
• Subjects: Cytology -- Periodicals; Cell Biology; Cytology; Periodicals; Electronic journals -- Sciences; Electronic journals -- Biology; Periodicals; 571.6
• DOI: 10.1155/2012/273549
• Languages: English
• ISSNs: 1687-8876

Abstract

Abstract : S-Glutathionylation of cysteine residues within target proteins is a posttranslational modification that alters structure and function. We have shown that S-glutathionylation of protein disulfide isomerase (PDI) disrupts protein folding and leads to the activation of the unfolded protein response (UPR). PDI is a molecular chaperone for estrogen receptor alpha ( ER α ) . Our present data show in breast cancer cells that S-glutathionylation of PDI interferes with its chaperone activity and abolishes its capacity to form a complex with ER α . Such drug treatment also reverses estradiol-induced upregulation of c-Myc, cyclinD1, and P 21 Cip, gene products involved in cell proliferation. Expression of an S-glutathionylation refractory PDI mutant diminishes the toxic effects of PABA/NO. Thus, redox regulation of PDI causes its S-glutathionylation, thereby mediating cell death through activation of the UPR and abrogation of ER α stability and signaling.