Endoplazmik retikulum stresi ve katlanmamış protein cevabı

Year 2012, Volume: 29 Issue: 2, 95 - 100, 23.02.2012

Aynur Düzgün Hasan Alaçam , Ali Okuyucu

Abstract

Hücre içerisinde bir çok önemli görevi bulunan endoplazmik retikulumun (ER) bir diğer önemli görevi de protein katlanmasının sağlanmasıdır. ER’de protein katlanmasının gerçekleşmesini sağlayan glukoz düzenleyici protein 78, glukoz düzenleyici protein 94, lektin benzeri proteinler ve foldazlar bulunmaktadır. ER fonksiyon kapasitesini aşan fizyolojik veya patolojik durumlarda lümende katlanmamış ya da yanlış katlanmış protein birikimi meydana gelir ve bu durum ER stresi olarak isimlendirilmektedir. ER stresi hücre içerisinde oluştuktan sonra hücrenin hayati fonksiyonlarını devam ettirebilmek için katlanmamış protein cevabı (UPR) adı verilen sinyal yolakları devreye girmektedir. Protein kinaz RNA (PKR) benzeri ER kinaz (PERK), aktive edici transkripsiyon faktörü (ATF6), inozitol gerektiren kinaz 1 (IRE1) yolakları UPR sinyal yolaklarının başlıcalarıdır.

Endoplasmic reticulum stress and unfolded protein response

Another important function of the endoplasmic reticulum (ER), which has many important tasks in the cell, is to ensure the protein folding. In ER, there are glucose regulated protein 78, glucose regulated protein 94, lectin like proteins and foldases, which enable the protein folding. In case of physiological and pathological situations that exceed the function capacity of ER, unfolded or misfolded protein accumulation occurs in lumen and this case is named as ER stress. After the ER stress occurs in the cell, the signal pathways named unfolded protein response (UPR) step in for the continuance of the vital functions of the cell. Major UPR signal pathways include protein kinase RNA (PKR) like ER kinase (PERK), activating transcription factor 6 (ATF6), j requiring kinase 1 (IRE1).

J. Exp. Clin. Med., 2012; 29:95-100

Keywords

Endoplazmik retikulum; Grp78; Grp94; PERK; ATF6; IRE (Endoplasmic reticulum; Grp78; Grp94; PERK; ATF6; IRE1)

References

• Argon, Y., Simen, B.B., 1999. GRP94, an ER chaperone with protein and peptide binding properties. Semin. Cell Dev. Biol. 10, 495-505.
• Bodsch, W., Takahashi, K., Barbier, A., Ophoff, B.G., Hossmann, K.A., 1985. Cerebral protein synthesis and ischemia. Prog. Brain Res. 63, 197-210.
• Buck, T.M., Wright C.M., Brodsky, J.L., 2007. The activities and function of molecular chaperones in the endoplasmic reticulum. Semin. Cell Dev. Biol. 18, 751-761.
• Calfon, M., Zeng, H., Urano, F.,Till, J.H., Hubbard, S.R., Harding, H.P.,Clark, S.G., Ron, D., 2002. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 415, 92-96.
• Chakrabarti, A., Chen, A.W., Varner, J.D., 2011. A review of the mammalian unfolded protein response. Biotechnol. Bioeng.108, 2777-2793.
• Conn, K.J., Gao, W.W., Ullman, M.D., McKeon-O'Malley, C., Eisenhauer, P.B., Fine, R.E., Wells, J.M., 2002. Specific up-regulation of GADD153/CHOP in 1-methyl-4-phenyl-pyridinium-treated SH-SY5Y cells. J.Neurosci Res. 68, 755-760.
• Corbett, E.F., Oikawa, K., Francois, P.,Tessier, D.C., Kay, C., Bergeron, J.J.M., Thomas, D.Y., Krause, K.H., Michalak, M., 1999. Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J. Biol. Chem. 274, 6203-6211.
• Delepine, M., Nicolino, M., Barrett, T., Golamaully, M., Mark, Lathrop, G., Julier, J., 2000. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat. Genet. 25, 406-409.
• Dobson, C.M., Sali A., Karplus, M., 1998. Protein folding: A perspective from theory and experiment. Angew. Chem. Int. Edit. 37, 868-893.
• Doutheil, J., Treiman, M., Oschlies, U., Paschen, W., 1999. Recovery of neuronal protein synthesis after irreversible inhibition of the endoplasmic reticulum calcium pump. Cell Calcium. 25, 419-428.
• Eikelboom, J.W., Lonn, E., Genest, J., Hankey, G., Yusuf, S., 1999. Homocysteine and cardiovasscular disease: A critical review of the epidemiologic evidence. Ann. Intern. Med. 131, 363-375.
• Ellgaard, L., Molinari, M., Helenius, A., 1999. Setting the standards: Quality control in the secretory pathway. Science. 286, 1882-1888.
• Fernandez, P.M., Tabbara, S.O., Jacobs, L.K., Manning, F.C.R., Tsangaris, T.N., Schwartz, A.M., Kennedy, K.A., Patierno, S. R., 2000. Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions. Breast Cancer Res. Treat. 59, 15-26.
• Gass, J.N., Gifford, N.M., Brewer, J.W., 2002. Activation of an unfolded protein response during differentiation of antibody-secreting B cells. J. Biol. Chem. 277, 49047-49054.
• Harding, H.P., Ron, D., 2002. Endoplasmic reticulum stres and the development of diabetes. Diabetes. 51, S455-S461.
• Harding, H.P., Zhang, Y., Ron, D., 1999. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 397, 271-274.
• Harding, H.P., Zeng, H., Zhang, Y., Jungries, R., Chung, P., Plesken, H., Sabatini, D.D., Ron, D., 2001. Diabetes Mellitus and exocrine pancreatic dysfunction in PERK -/- mice reveals a role for translationl control in secretory cell survival. Mol. Cell. 7, 1153-1163.
• Hendershot, L.M., 2004. The ER chaperone BiP is a master regulator of ER function. Mt. Sinai J. Med. 71, 289-297.
• Horwich, A., 2002. Protein aggregation in disease: A role for folding intermediates forming specific multimeric interactions. J. Clin. Invest. 110, 1221-1232.
• Hu, B.R., Janelidze, S., Ginsberg, M.D., Busto, R, Perez-Pinzon, M., Sick, T.J., Siesjö, B.K., Liu, C.L., 2001. Protein aggregation after focal brain ischemia and reperfusion. J. Cereb. Blood Flow Metab. 21, 865-875.
• Huang, R.F., Huang, S.M., Lin, B.S., Wei, J.S., Liu, T.Z., 2001. Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci. 68, 2799-2811.
• Iwakoshi, N.N., Lee, A.H., Vallabhajosyula, P., Otipoby, K.L., Rajewsky, K., Glimcher, L.H., 2003. Plasma cell differantiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat. Immunol. 4, 321-329.
• Kapoor, A., Sanyal, A.J., 2009. Endoplasmic reticulum stress and the unfolded protein response. Clin. Liver Dis.13, 581-590.
• Kaufman, R.J., 1999. Stress signaling from the lumen of the endoplasmic reticulum: Coordination of gene transcriptional and translational controls. Gene. Dev. 13, 1211-1233.
• Kaufman, R.J., 2002. Orchestrating the unfolded protein response in health and disease. J. Clin. Invest. 110, 1389-1398.
• Koritzinsky, M., Magagnin, M.G., van den Beucken, T., Seigneuric, R., Savelkouls, K., Dostie, J., Pyronnet, S., Kaufman, R.J., Weppler, S.A.,
• Voncken, J.W., Lambin, P., Koumenis, C., Sonenberg, N., Wouters, B.G., 2006. Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control. Embo J. 25, 1114-1125.
• Koumenis, C., Naczki, C., Koritzinsky, M., Rastani, S., Diehl, A., Sonenberg, N., Koromilas, A., Wouters, B.G., 2002. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol. Cell Biol. 22, 7405-7416.
• Lai, E.D., Teodoro, T., Volchuk, A., 2007. Endoplasmic reticulum stress: Signaling the unfolded protein response. Physiology. 22, 193-201.
• Lee, A.S., 2007. GRP78 induction in cancer: Therapeutic and prognostic implications. Cancer Res. 67, 3496-3499.
• Lee, E., Nichols, P., Spicer, D., Groshen, S., Yu, M.C., Lee, A.S., 2006. GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer. Cancer Res. 66, 7849-7853.
• Little, E., Ramakrishnan, M., Roy, B., Gazit, G., Lee, A.S., 1994. The glucose-regulated proteins (GRP78 and GRP94): Functions, gene regulation, and applications. Crit. Rev. Eukar. Gene . 4,1-18.
• Liu, C.Y., Schroder, M., Kaufman R.J., 2000. Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 275, 24881-24885.
• Ma, Y., Hendershot, L.M., 2003. Delineation of a negative feedback regulatory loop that controls protein translation during endoplasmic reticulum stress. J. Biol. Chem. 278, 34864-34873.
• Maattanen, P., Gehring, K., Bergeron, J.J., Thomas, D.Y., 2010. Protein quality control in the ER: The recognition of misfolded proteins. Semin. Cell Dev. Biol. 21, 500-511.
• Misra, U.K., Deedwania, R., Pizzo, S.V., 2006. Activation and cross-talk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78. J. Biol. Chem. 281, 13694-13707.
• Mori, K., 2000. Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell. 101, 451-454.
• Naidoo, N., 2009. ER and aging-Protein folding and the ER stress response. Ageing Res. Rev. 8, 150-159.
• Nechushtan, A., Smith, C.L., Hsu, Y.T., Youle, R.J., 1999. Conformation of the Bax C-terminus regulates subcellular location and cell death. Embo J. 18, 2330-2341.
• Pollard, M.G., Travers, K.J., Weissman, J.S., 1998. Ero1p: A novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum. Mol. Cell.1, 171-182.
• Outinen, P.A., Sood, S.K., Pfeifer, S.I., Pamidi, S., Podor, T.J., Li, J., Weitz, J.I., Austin, R.C., 1999. Homocysteine-induced endoplasmic reticulum stres and growth arrest leads to spesific changes in gene expression in human vascular endothelial cells. Blood. 94, 959-967.
• Reddy, R.K., Mao, C.H., Baumeister, P., Austin, R.C., Kaufman, R.J., Lee, A.S., 2003. Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors-Role of ATP binding site in suppression of caspase-7 activation. J. Biol. Chem. 278, 20915-20924.
• Reimold, A.M., Iwakoshi, N.N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E.M., Friend, D., Grusby, M.J., Alt, F., Glimcher, L.H., 2001. Plasma cell differentiation requires the transcription factor XBP-1. Nature. 412, 300-307.
• Ron, D., 2002. Translational control in the endoplasmic reticulum stress response. J. Clin. Invest. 110, 1383-1388.
• Ron, D., Walter, P., 2007. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519-529.
• Rutkowski, D.T., Kaufman, R.J., 2004. A trip to the ER: Coping with stress. Trends Cell Biol. 14, 20-28.
• Scheuner, D., Song, B., McEwen, E., Liu, C., Laybutt, R., Gillespie, P., Saunders, T., Bonner-Weir, S., Kaufman, R.J., 2001. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell. 7, 1165-1176.
• Schroder, M., Kaufman, R.J., 2005. The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739-789.
• Sevier, C.S., Cuozzo, J.W., Vala, A., Aslund, F., Kaiser, C.A., 2001. A flavoprotein oxidase defines a new endoplasmic reticulum pathway for biosynthetic disulphide bond formation. Nat. Cell Biol. 3, 874-882.
• Shen, X., Zhang, K., Kaufman, R.J., 2004. The Unfolded protein response- a stress signaling pathway of the endoplasmic reticulum. J. Chem. Neuroanat. 28, 79-92.
• Stevens, F.J., Argon, Y., 1999. Protein folding in the ER. Semin. Cell Dev. Biol. 10, 443-454.
• Thilmann, R., Xie, Y., Kleihues, P., Kiessling, M., 1986. Persistent inhibition of protein synthesis preceeds delayed neuronal death in postischemic gerbil hippocampus. Acta Neuropathol. 71, 88-93.
• Tu, B.P., Ho-Schleyer, S.C., Travers, K.J., Weissman, J.S., 2000. Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science. 290, 1571-1574.
• Wang, M., Wey, S., Zhang, Y., Ye, R., Lee, A.S., 2009. Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxid. Redox Sign. 11, 2307-2316.
• Wei, M.C., Zong, W.X., Cheng, E.H., Lindsten, T., Panoutsakopoulou, V., Ross, A.J., Roth, K.A., Mac-Gregor, G.R., Thompson, C.B., Korsmeyer, S.J., 2001. Proapoptotic Bax and Bak: A requisite gateway to mitochondrial dysfunction and death. Science. 292, 727-730.
• Wormald, M.R., Dwek, R.A., 1999. Glycoproteins: Glycan presentation and protein-fold stability. Structure Fold. Des. 7, R155-R160.
• Yoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., Negishi, M., Mori, K., 2001. Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response. Mol. Cell Biol. 21, 1239-1248.
• Zhang, K., Kaufman, R.J., 2008. From endoplasmic-reticulum stress to the inflammatory response. Nature. 454, 455-462.
• Zhang, C., Cai, Y., Adachi, M.T., Oshiro, S., Aso, T., Kaufman, R.J., Kitajima, S., 2001. Homocysteine induces programmed cell death through activation of the unfolded protein response. J. Biol. Chem. 276, 35867-35874.