S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function
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 (U...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/273549 |
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| author | Ying Xiong Yefim Manevich Kenneth D. Tew Danyelle M. Townsend |
| author_facet | Ying Xiong Yefim Manevich Kenneth D. Tew Danyelle M. Townsend |
| author_sort | Ying Xiong |
| collection | DOAJ |
| description | 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 (ERα). 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 ERα. Such drug treatment also reverses estradiol-induced upregulation of c-Myc, cyclinD1, and P21Cip, 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 ERα stability and signaling. |
| format | Article |
| id | doaj-art-f65469732f0f4f74a95c8c1ad9ed547f |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-f65469732f0f4f74a95c8c1ad9ed547f2025-02-03T06:04:58ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/273549273549S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and FunctionYing Xiong0Yefim Manevich1Kenneth D. Tew2Danyelle M. Townsend3Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USAS-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 (ERα). 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 ERα. Such drug treatment also reverses estradiol-induced upregulation of c-Myc, cyclinD1, and P21Cip, 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 ERα stability and signaling.http://dx.doi.org/10.1155/2012/273549 |
| spellingShingle | Ying Xiong Yefim Manevich Kenneth D. Tew Danyelle M. Townsend S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function International Journal of Cell Biology |
| title | S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function |
| title_full | S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function |
| title_fullStr | S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function |
| title_full_unstemmed | S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function |
| title_short | S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function |
| title_sort | s glutathionylation of protein disulfide isomerase regulates estrogen receptor α stability and function |
| url | http://dx.doi.org/10.1155/2012/273549 |
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