Roles of CHOP/GADD153 in endoplasmic reticulum stress

Cell Death and Differentiation - Tập 11 Số 4 - Trang 381-389 - 2004
Seiichi Oyadomari1,2, Masataka Mori1
1Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
2Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation Trends. Cell Biol. 10: 524–530

Kaufman RJ (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13: 1211–1233

Mori K (2000) Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101: 451–454

Ron D (2002) Translational control in the endoplasmic reticulum stress response. J. Clin. Invest. 110: 1383–1388

Kaufman RJ (2002) Orchestrating the unfolded protein response in health and disease. J. Clin. Invest. 110: 1389–1398

Harding HP, Calfon M, Urano F, Novoa I and Ron D (2002) Transcriptional and translational control in the mammalian unfolded protein response. Annu. Rev. Cell Dev. Biol. 18: 575–599

Kozutsumi MY, Segal M, Normington K, Gething MJ and Sambrook J (1988) The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332: 462–464

Yoshida H, Haze K, Yanagi H, Yura T and Mori K (1998) Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J. Biol. Chem. 273: 33741–33749

Caspersen C, Pedersen PS and Treiman M (2000) The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein. J. Biol. Chem. 275: 22363–22372

Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T and Leiden JM (2003) An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11: 619–633

Kopito RR (1997) ER quality control: the cytoplasmic connection. Cell 88: 427–430

Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS and Walter P (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101: 249–258

Yoshida H, Matsui T, Hosokawa N, Kaufman RJ, Nagata K and Mori K (2003) A time-dependent phase shift in the mammalian unfolded protein response. Dev. Cell 4: 265–271

Pahl HL, Sester M, Burgert HG and Baeuerle PA (1996) Activation of transcription factor NF-kappaB by the adenovirus E3/19 K protein requires its ER retention. J. Cell Biol. 132: 511–522

Jiang HY, Wek SA, McGrath BC, Scheuner D, Kaufman RJ, Cavener DR and Wek RC (2003) Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses. Mol. Cell. Biol. 23: 5651–5663

Ferri KF and Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat. Cell Biol. 3: E255–E263

Oyadomari S, Araki E and Mori M (2002) Endoplasmic reticulum stress-mediated apoptosis in pancreatic beta-cells. Apoptosis 7: 335–345

Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP and Ron D (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287: 664–666

Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, Hori S, Kakizuka A and Ichijo H (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16: 1345–1355

Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA and Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403: 98–103

Fischer H, Koenig U, Eckhart L and Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem. Biophys. Res. Commun. 293: 722–726

Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB and Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292: 727–730

Matsumoto M, Minami M, Takeda K, Sakao Y and Akira S (1996) Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS Lett. 395: 143–147

Ron D and Habener JF (1992) CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 6: 439–453

Ubeda M, Wang XZ, Zinszner H, Wu I, Habener JF and Ron D (1996) Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element. Mol. Cell. Biol. 16: 1479–1489

Wang XZ and Ron D (1996) Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP kinase. Science 272: 1347–1349

Maytin EV, Ubeda M, Lin JC and Habener JF (2001) Stress-inducible transcription factor CHOP/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms. Exp. Cell Res. 267: 193–204

Barone MV, Crozat A, Tabaee A, Philipson L and Ron D (1994) CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest. Genes Dev. 8: 453–464

Ubeda M, Vallejo M and Habener JF (1999) CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins. Mol. Cell. Biol. 19: 7589–7599

Fornace Jr AJ, Alamo Jr I and Hollander MC (1988) DNA damage-inducible transcripts in mammalian cells. Proc. Natl. Acad. Sci. USA 85: 8800–8804

Wang XZ, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi LJ, Boorstein R, Kreibich G, Hendershot LM and Ron D (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol. Cell. Biol. 16: 4273–4280

Okada T, Yoshida H, Akazawa R, Negishi M and Mori K (2002) Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem. J. 366: 585–594

Bertolotti A, Zhang Y, Hendershot LM, Harding HP and Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2: 326–332

Sommer T and Jarosch E (2002) BiP binding keeps ATF6 at bay. Dev. Cell 3: 1–2

Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS and Goldstein JL (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6: 1355–1364

Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M and Mori K (2000) ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell. Biol. 20: 6755–6767

Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M and 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

Yoshida H, Matsui T, Yamamoto A, Okada T and Mori K (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107: 881–891

Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG and Ron D (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415: 92–96

Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, Yoshida H, Mori K and Kaufman RJ (2002) IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 16: 452–466

Wang Y, Shen J, Arenzana N, Tirasophon W, Kaufman RJ and Prywes R (2000) Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. J. Biol. Chem. 275: 27013–27020

Ubeda M and Habener JF (2000) CHOP gene expression in response to endoplasmic-reticular stress requires NFY interaction with different domains of a conserved DNA-binding element. Nucleic Acids Res. 28: 4987–4997

Roy B and Lee AS (1999) The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex. Nucleic Acids Res. 27: 1437–1443

Bruhat A, Jousse C, Carraro V, Reimold AM, Ferrara M and Fafournoux P (2000) Amino acids control mammalian gene transcription: activating transcription factor 2 is essential for the amino acid responsiveness of the CHOP promoter. Mol. Cell. Biol. 20: 7192–7204

Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S and Kaufman RJ (2001) Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7: 1165–1176

Harding HP, Novoa II, Zhang Y, Zeng H, Wek R, Schapira M and Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6: 1099–1108

Chen BP, Wolfgang CD and Hai T (1996) Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10. Mol. Cell. Biol. 16: 1157–1168

Wolfgang CD, Chen BP, Martindale JL, Holbrook NJ and Hai T (1997) gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3. Mol. Cell. Biol. 17: 6700–6707

Fawcett TW, Martindale JL, Guyton KZ, Hai T and Holbrook NJ (1999) Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress response. Biochem. J. 339: 135–141

Estes SD, Stoler DL and Anderson GR (1995) Normal fibroblasts induce the C/EBP beta and ATF-4 bZIP transcription factors in response to anoxia. Exp. Cell Res. 220: 47–54

Bartlett JD, Luethy JD, Carlson SG, Sollott SJ and Holbrook NJ (1992) Calcium ionophore A23187 induces expression of the growth arrest and DNA damage inducible CCAAT/enhancer-binding protein (C/EBP)-related gene, gadd153. Ca2+ increases transcriptional activity and mRNA stability. J. Biol. Chem. 267: 20465–20470

Bruhat A, Jousse C, Wang XZ, Ron D, Ferrara M and Fafournoux P (1997) Amino acid limitation induces expression of CHOP, a CCAAT/enhancer binding protein-related gene, at both transcriptional and post-transcriptional levels. J. Biol. Chem. 272: 17588–17593

Schmitt-Ney M and Habener JF (2000) CHOP/GADD153 gene expression response to cellular stresses inhibited by prior exposure to ultraviolet light wavelength band C (UVC). Inhibitory sequence mediating the UVC response localized to exon 1. J. Biol. Chem. 275: 40839–40845

Jousse C, Bruhat A, Carraro V, Urano F, Ferrara M, Ron D and Fafournoux P (2001) Inhibition of CHOP translation by a peptide encoded by an open reading frame localized in the chop 5′UTR. Nucleic Acids Res. 29: 4341–4351

Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K, Minowa O, Miyazono K, Noda T and Ichijo H (2001) ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2: 222–228

Oyadomari S, Takeda K, Takiguchi M, Gotoh T, Matsumoto M, Wada I, Akira S, Araki E and Mori M (2001) Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc. Natl. Acad. Sci. USA 98: 10845–10850

Gotoh T, Oyadomari S Mori K and Mori M (2002) Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP. J. Biol. Chem. 277: 12343–12350

Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL and Ron D (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12: 982–995

Oyadomari S, Koizumi A, Takeda K, Gotoh T, Akira S, Araki E and Mori M (2002) Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J. Clin. Invest. 109: 525–532

Wang XZ, Kuroda M, Sok J, Batchvarova N, Kimmel R, Chung P, Zinszner H and Ron D (1998) Identification of novel stress-induced genes downstream of chop. EMBO J. 17: 3619–3630

Sok J, Wang XZ, Batchvarova N, Kuroda M, Harding H and Ron D (1999) CHOP-dependent stress-inducible expression of a novel form of carbonic anhydrase VI. Mol. Cell. Biol. 19: 495–504

McCullough KD, Martindale JL, Klotz LO, Aw TY and Holbrook NJ (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol. Cell. Biol. 21: 1249–1259

Gotoh T, Takeda K, Oyadomari S and Mori M . hsp70-DnaJ chaperone pair prevents nitric oxide-, CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ. in press

Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler WJ and Timchenko NA (2001) C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4. Mol. Cell 8: 817–828

Wang H, Goode T, Iakova P, Albrecht JH and Timchenko NA (2002) C/EBPalpha triggers proteasome-dependent degradation of cdk4 during growth arrest. EMBO J. 21: 930–941

Kawai T, Matsumoto M, Takeda K, Sanjo H and Akira S (1998) ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Mol. Cell. Biol. 18: 1642–1651

Reimold AM, Etkin A, Clauss I, Perkins A, Friend DS, Zhang J, Horton HF, Scott A, Orkin SH, Byrne MC, Grusby MJ and Glimcher LH (2000) An essential role in liver development for transcription factor XBP-1. Genes Dev. 14: 152–157

Harding HP, Zeng H, Zhang Y, Jungries R, Chung P, Plesken H, Sabatini DD and Ron D (2001) Diabetes mellitus and exocrine pancreatic dysfunction in perk−/− mice reveals a role for translational control in secretory cell survival. Mol. Cell 7: 1153–1163

Zhang P, McGrath B, Li S, Frank A, Zambito F, Reinert J, Gannon M, Ma K, McNaughton K and Cavener DR (2002) The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol. Cell. Biol. 22: 3864–3874

Reimold AM, Iwakoshi NN, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, Gravallese EM, Friend D, Grusby MJ, Alt F and Glimcher LH (2001) Plasma cell differentiation requires the transcription factor XBP-1. Nature 412: 300–307

Harding HP, Zhang Y, Bertolotti A, Zeng H and Ron D (2000) Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5: 897–904

Coutts M, Cui K, Davis KL, Keutzer JC and Sytkowski AJ (1999) Regulated expression and functional role of the transcription factor CHOP (GADD153) in erythroid growth and differentiation. Blood 93: 3369–3378

Maytin EV and Habener JF (1998) Transcription factors C/EBP alpha, C/EBP beta, and CHOP (Gadd153) expressed during the differentiation program of keratinocytes in vitro and in vivo. J. Invest. Dermatol. 110: 238–246

Mathis D, Vence L and Benoist C (2001) Beta-cell death during progression to diabetes. Nature 414: 792–798

Kaufman RJ, Scheuner D, Schroder M, Shen X, Lee K, Liu CY and Arnold SM (2002) The unfolded protein response in nutrient sensing and differentiation. Nat. Rev. Mol. Cell. Biol. 3: 411–421

Harding HP and Ron D (2002) Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes 51 (Suppl 3): S455–S461

Araki E, Oyadomari S and Mori M (2003) Endoplasmic reticulum stress and diabetes mellitus. Intern. Med. 42: 7–14

Thornton C (1997) Autopsy findings in the Wolcott–Rallison syndrome. Pediatr. Pathol. Lab. Med. 17: 487–496

Nicolino M, Delepine M, Barrett T, Golamaully M, Lathrop GM and Julier C (2000) EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott–Rallison syndrome. Nat. Genet. 25: 406–409

Eizirik DL and Mandrup-Poulsen T (2001) A choice of death – the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44: 2115–2133

Heller B, Wang ZQ, Wagner EF, Radons J, Burkle A, Fehsel K, Burkart V and Kolb H (1995) Inactivation of the poly(ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells. J. Biol. Chem. 270: 11176–11180

Messmer UK and Brune B (1996) Nitric oxide-induced apoptosis: p53-dependent and p53-independent signalling pathways. Biochem. J. 319: 299–305

Viner RI, Ferrington DA, Williams TD, Bigelow DJ and Schoneich C (1999) Protein modification during biological aging: selective tyrosine nitration of the SERCA2a isoform of the sarcoplasmic reticulum Ca2+-ATPase in skeletal muscle. Biochem. J. 340: 657–669

Xu KY, Huso DL, Dawson TM, Bredt DS and Becker LC (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc. Natl. Acad. Sci. USA 96: 657–662

Xu L, Eu JP, Meissner G and Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279: 234–237

Cardozo AK, Kruhoffer M, Leeman R, Orntoft T and Eizirik DL (2001) Identification of novel cytokine-induced genes in pancreatic beta-cells by high-density oligonucleotide arrays. Diabetes 50: 909–920

Yoshioka M, Kayo T, Ikeda T and Koizumi A (1997) A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46: 887–894

Kayo T and Koizumi A (1998) Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period. J. Clin. Invest. 101: 2112–2118

Wang J, Takeuchi T, Tanaka S, Kubo SK, Kayo T, Lu D, Takata K, Koizumi A and Izumi T (1999) A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse. J. Clin. Invest. 103: 27–37

Leroux L, Desbois P, Lamotte L, Duvillie B, Cordonnier N, Jackerott M, Jami J, Bucchini D and Joshi RL (2001) Compensatory responses in mice carrying a null mutation for Ins1 or Ins2. Diabetes 50 (Suppl 1): S150–S153

Hu BR, Janelidze S, Ginsberg MD, Busto R, Perez-Pinzon M, Sick TJ, Siesjo BK and Liu CL (2001) Protein aggregation after focal brain ischemia and reperfusion. J. Cereb. Blood Flow Metab. 21: 865–875

Kumar R, Azam S, Sullivan JM, Owen C, Cavener DR, Zhang P, Ron D, Harding HP, Chen JJ, Han A, White BC, Krause GS and DeGracia DJ (2001) Brain ischemia and reperfusion activates the eukaryotic initiation factor 2 alpha kinase, PERK. J. Neurochem. 77: 1418–1421

Paschen W, Gissel C, Linden T, Althausen S and Doutheil J (1998) Activation of gadd153 expression through transient cerebral ischemia: evidence that ischemia causes endoplasmic reticulum dysfunction. Brain Res. Mol. Brain Res. 60: 115–122

Jin K, Mao XO, Eshoo MW, Nagayama T, Minami M, Simon RP and Greenberg DA (2001) Microarray analysis of hippocampal gene expression in global cerebral ischemia. Ann. Neurol. 50: 93–103

Doutheil J, Althausen S, Treiman M and Paschen W (2000) Effect of nitric oxide on endoplasmic reticulum calcium homeostasis, protein synthesis and energy metabolism. Cell Calcium 27: 107–115

Kohno K, Higuchi T, Ohta S, Kumon Y and Sakaki S (1997) Neuroprotective nitric oxide synthase inhibitor reduces intracellular calcium accumulation following transient global ischemia in the gerbil. Neurosci. Lett. 224: 17–20

Iadecola C, Zhang F, Casey R, Nagayama M and Ross ME (1997) Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J. Neurosci. 17: 9157–9164

Tajiri S, Oyadomari S, Yano S, Morioka M, Gotoh T, Hamada J-I, Ushio Y and Mori M . Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP. Cell Death Differ in press

Milhavet O, Martindale JL, Camandola S, Chan SL, Gary DS, Cheng A, Holbrook NJ and Mattson MP (2002) Involvement of Gadd153 in the pathogenic action of presenilin-1 mutations. J. Neurochem. 83: 673–681

Katayama T, Imaizumi K, Sato N, Miyoshi K, Kudo T, Hitomi J, Morihara T, Yoneda T, Gomi F, Mori Y, Nakano Y, Takeda J, Tsuda T, Itoyama Y, Murayama O, Takashima A, St George-Hyslop P, Takeda M and Tohyama M (1999) Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response. Nat. Cell Biol. 1: 479–485

Sato N, Urano F, Yoon Leem J, Kim SH, Li M, Donoviel D, Bernstein A, Lee AS, Ron D, Veselits ML, Sisodia SS and Thinakaran G (2000) Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression. Nat. Cell Biol. 2: 863–870

Ryu EJ, Harding HP, Angelastro JM, Vitolo OV, Ron D and Greene LA (2002) Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson's disease. J. Neurosci. 22: 10690–10698

Holtz WA and O'Malley KL (2003) Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J. Biol. Chem. 278: 19367–19377

Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM and Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat. Med. 5: 1403–1409

Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K and Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25: 302–305

Imai Y, Soda M and Takahashi R (2000) Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 275: 35661–35664

Petrucelli L, O'Farrell C, Lockhart PJ, Baptista M, Kehoe K, Vink L, Choi P, Wolozin B, Farrer M, Hardy J and Cookson MR (2002) Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36: 1007–1019