Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 52, 2012, Pages 21486-21491

  Harbut, Michael B ^a,g   Patel, Bhumit A ^a   Yeung, Bryan K S ^b   McNamara, Case W ^c   Bright, A Taylor ^d   Ballard, Jaime ^c   Supek, Frantisek ^c   Golde, Todd E ^e   Winzeler, Elizabeth A ^c,f   Diagana, Thierry T ^b   Greenbaum, Doron C ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

^c GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^f UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^g California Institute for Biomedical Research   (United States)

Author keywords

Intramembrane proteolysis; Small molecule; Target validation

Indexed keywords

ANTIPARASITIC AGENT; NITD 731; PEPTIDES AND PROTEINS; PROTEINASE INHIBITOR; SIGNAL PEPTIDE PEPTIDASE; UNCLASSIFIED DRUG;

ARTICLE; BIOINFORMATICS; DRUG DESIGN; DRUG TARGETING; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; ENZYME INHIBITION; MALARIA FALCIPARUM; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN TARGETING;

ANIMALS; ANTIPARASITIC AGENTS; ASPARTIC ACID ENDOPEPTIDASES; BASE SEQUENCE; COMPUTATIONAL BIOLOGY; DRUG DESIGN; DRUG RESISTANCE; ENDOPLASMIC RETICULUM STRESS; ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION; HEP G2 CELLS; HUMANS; LIFE CYCLE STAGES; LIVER; MOLECULAR SEQUENCE DATA; PARASITES; PLASMODIUM FALCIPARUM; PROTEASE INHIBITORS; PROTEASOME INHIBITORS; PROTEOLYSIS; PROTEOME; SMALL MOLECULE LIBRARIES; TOXOPLASMA; TRYPANOSOMA CRUZI;

EUKARYOTA; PLASMODIUM FALCIPARUM; PROTOZOA;

EID: 84871826750     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1216016110     Document Type: Article

References (42)

1. Dondorp AM, et al. (2011) The threat of artemisinin-resistant malaria. N Engl J Med 365(12):1073-1075.
2. Maier AG, Cooke BM, Cowman AF, Tilley L (2009) Malaria parasite proteins that remodel the host erythrocyte. Nat Rev Microbiol 7(5):341-354.
3. Smith MH, Ploegh HL, Weissman JS (2011) Road to ruin: Targeting proteins for degradation in the endoplasmic reticulum. Science 334(6059):1086-1090.
4. Walter P, Ron D (2011) The unfolded protein response: From stress pathway to homeostatic regulation. Science 334(6059):1081-1086.
5. Travers KJ, et al. (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101(3):249-258.
6. Carvalho P, Goder V, Rapoport TA (2006) Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell 126(2):361-373. (Pubitemid 44092963)
7. Christianson JC, et al. (2012) Defining human ERAD networks through an integrative mapping strategy. Nat Cell Biol 14(1):93-105.
8. Bozdech Z, et al. (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol 1(1):E5.
9. Ward P, Equinet L, Packer J,Doerig C (2004) Protein kinases of the human malaria parasite Plasmodium falciparum: The kinome of a divergent eukaryote. BMC Genomics 5:79.
10. Fennell C, et al. (2009) PfeIK1, a eukaryotic initiation factor 2alpha kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation. Malar J 8:99.
11. Zhang M, et al. (2012) PK4, a eukaryotic initiation factor 2α(eIF2α) kinase, is essential for the development of the erythrocytic cycle of Plasmodium. Proc Natl Acad Sci USA 109(10):3956-3961.
12. Gosline SJ, et al. (2011) Intracellular eukaryotic parasites have a distinct unfolded protein response. PLoS ONE 6(4):e19118.
13. Egorin MJ, et al. (2002) Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats. Cancer Chemother Pharmacol 49(1):7-19.
14. Banumathy G, Singh V, Pavithra SR, Tatu U (2003) Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. J Biol Chem 278(20):18336-18345. (Pubitemid 36799454)
15. Pallavi R, et al. (2010) Heat shock protein 90 as a drug target against protozoan infections: Biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. J Biol Chem 285(49):37964-37975.
16. Hoffstrom BG, et al. (2010) Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins. Nat Chem Biol 6(12):900-906.
17. Chou TF, et al. (2011) Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci USA 108(12):4834-4839.
18. Chung DW, Ponts N, Prudhomme J, Rodrigues EM, Le Roch KG (2012) Characterization of the ubiquitylating components of the human malaria parasite' s protein degradation pathway. PLoS ONE 7(8):e43477.
19. Weihofen A, Binns K, LembergMK, Ashman K, Martoglio B (2002) Identification of signal peptide peptidase, a presenilin-type aspartic protease. Science 296(5576):2215-2218. (Pubitemid 34680305)
20. Loureiro J, et al. (2006) Signal peptide peptidase is required for dislocation from the endoplasmic reticulum. Nature 441(7095):894-897.
21. Stagg HR, et al. (2009) The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER. J Cell Biol 186(5):685-692.
22. Lee SO, et al. (2010) Protein disulphide isomerase is required for signal peptide peptidase-mediated protein degradation. EMBO J 29(2):363-375.
23. Bagola K, Mehnert M, Jarosch E, Sommer T (2011) Protein dislocation from the ER. Biochim Biophys Acta 1808(3):925-936.
24. Crawshaw SG, Martoglio B, Meacock SL, High S (2004) A misassembled transmembrane domain of a polytopic protein associates with signal peptide peptidase. Biochem J 384(pt 1):9-17. (Pubitemid 39564156)
25. Schrul B, Kapp K, Sinning I, Dobberstein B (2010) Signal peptide peptidase (SPP) assembles with substrates and misfolded membrane proteins into distinct oligomeric complexes. Biochem J 427(3):523-534.
26. Krawitz P, et al. (2005) Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3. J Biol Chem 280(47):39515-39523. (Pubitemid 41713910)
27. Casso DJ, Tanda S, Biehs B, Martoglio B, Kornberg TB (2005) Drosophila signal peptide peptidase is an essential protease for larval development. Genetics 170(1):139-148. (Pubitemid 40799978)
28. Marapana DS, et al. (2012) Malaria parasite signal peptide peptidase is an ER-resident protease required for growth but not invasion. Traffic 13(11):1457-1465.
29. Booth C, Koch GL (1989) Perturbation of cellular calcium induces secretion of luminal ER proteins. Cell 59(4):729-737. (Pubitemid 19282880)
30. Srivastava IK, Rottenberg H, Vaidya AB (1997) Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. J Biol Chem 272(7):3961-3966. (Pubitemid 27078454)
31. Tiwari S, Weissman AM (2001) Endoplasmic reticulum (ER)-associated degradation of T cell receptor subunits. Involvement of ER-associated ubiquitin-conjugating enzymes (E2s). J Biol Chem 276(19):16193-16200.
32. Zhong X, Pittman RN (2006) Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates. Hum Mol Genet 15(16):2409-2420. (Pubitemid 44288695)
33. Li X, et al. (2009) Plasmodium falciparum signal peptide peptidase is a promising drug target against blood stage malaria. Biochem Biophys Res Commun 380(3):454-459.
34. Rottmann M, et al. (2010) Spiroindolones, a potent compound class for the treatment of malaria. Science 329(5996):1175-1180.
35. Nzila A, Mwai L (2010) In vitro selection of Plasmodium falciparum drug-resistant parasite lines. J Antimicrob Chemother 65(3):390-398.
36. Balu B, Shoue DA, Fraser MJ, Jr., Adams JH (2005) High-efficiency transformation of Plasmodium falciparum by the lepidopteran transposable element piggyBac. Proc Natl Acad Sci USA 102(45):16391-16396. (Pubitemid 41688924)
37. Meister S, et al. (2011) Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery. Science 334(6061):1372-1377.
38. Braakman I, Bulleid NJ (2011) Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem 80:71-99.
39. Wolfe MS (2008) Inhibition and modulation of gamma-secretase for Alzheimer's disease. Neurotherapeutics 5(3):391-398.
40. Weihofen A, et al. (2003) Targeting presenilin-type aspartic protease signal peptide peptidase with gamma-secretase inhibitors. J Biol Chem 278(19):16528-16533. (Pubitemid 36799513)
41. Sato T, et al. (2006) Signal peptide peptidase: Biochemical properties and modulation by nonsteroidal antiinflammatory drugs. Biochemistry 45(28):8649-8656. (Pubitemid 44078885)
42. Finn RD, Clements J, Eddy SR (2011) HMMER Web server: Interactive sequence similarity searching. Nucleic Acids Res 39(Web server issue):W29-W37.