Analysis of Proteolytic Processes and Enzymatic Activities in the Generation of Huntingtin N-Terminal Fragments in an HEK293 Cell Model

PLoS ONE

Volumn 7, Issue 12, 2012, Pages

  Tebbenkamp, Andrew T N ^a,b   Crosby, Keith W ^a,b   Siemienski, Zoe B ^a,b   Brown, Hilda H ^a,b   Golde, Todd E ^a   Borchelt, David R ^a,b   Li, Xiao Jiang ^c  

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

^b UNIVERSITY OF FLORIDA   (United States)

^c EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALPAIN; CASPASE; CYSTEINE; EPITOPE; GAMMA SECRETASE; HUNTINGTIN; METALLOPROTEINASE;

AMINO ACID SUBSTITUTION; AMINO TERMINAL SEQUENCE; ANTIBODY LABELING; ANTIGEN BINDING; ARTICLE; BIOINFORMATICS; CARBOXY TERMINAL SEQUENCE; CELL STRAIN HEK293; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME SPECIFICITY; EPITOPE MAPPING; GENE EXPRESSION; GENETIC ANALYSIS; HUMAN; HUMAN CELL; MODEL; NUCLEOTIDE SEQUENCE; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEINASE INHIBITION;

CELL NUCLEUS; CYTOPLASM; HEK293 CELLS; HUMANS; HUNTINGTON DISEASE; NERVE TISSUE PROTEINS; PEPTIDE FRAGMENTS; PROTEOLYSIS;

EID: 84870933532     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0050750     Document Type: Article

References (49)

1. Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971-983.
2. de la Monte SM, Vonsattel J-P, Richardson EP, (1988) Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington's disease. J Neuropathol Exp Neurol 47: 516-525.
3. Myers RH, Vonsattel JP, Stevens TJ, Cupples LA, Richardson EP, et al. (1988) Clinical and neuropathologic assessment of severity in Huntington's disease. Neurology 38: 341-347.
4. Herndon ES, Hladik CL, Shang P, Burns DK, Raisanen J, et al. (2009) Neuroanatomic profile of polyglutamine immunoreactivity in Huntington disease brains. J Neuropathol Exp Neurol 68: 250-261.
5. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, et al. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277: 1990-1993.
6. Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, et al. (1999) Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J Neurosci 19: 2522-2534.
7. Lunkes A, Lindenberg KS, Ben Haiem L, Weber C, Devys D, et al. (2002) Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol Cell 10: 259-269.
8. Schilling G, Klevytska A, Tebbenkamp AT, Juenemann K, Cooper J, et al. (2007) Characterization of huntingtin pathologic fragments in human Huntington disease, transgenic mice, and cell models. J Neuropathol Exp Neurol 66: 313-320.
9. Landles C, Sathasivam K, Weiss A, Woodman B, Moffitt H, et al. (2010) Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease. J Biol Chem 285: 8808-8823.
10. Cooper JK, Schilling G, Peters MF, Herring WJ, Sharp AH, et al. (1998) Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet 7: 783-790.
11. Martindale D, Hackam A, Wieczorek A, Ellerby L, Wellington C, et al. (1998) Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet 18: 150-154.
12. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, et al. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87: 493-506.
13. Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, et al. (1999) Intranuclear inclusions and neuritic pathology in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 8: 397-407.
14. Slow EJ, van Raamsdonk J, Rogers D, Coleman SH, Graham RK, et al. (2003) Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12: 1555-1567.
15. Gray M, Shirasaki DI, Cepeda C, Andre VM, Wilburn B, et al. (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28: 6182-6195.
16. Heng MY, Detloff PJ, Albin RL, (2008) Rodent genetic models of Huntington disease. Neurobiol Dis 32: 1-9.
17. Woodman B, Butler R, Landles C, Lupton MK, Tse J, et al. (2007) The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes. Brain Res Bull 72: 83-97.
18. Kim YJ, Sapp E, Cuiffo BG, Sobin L, Yoder J, et al. (2006) Lysosomal proteases are involved in generation of N-terminal huntingtin fragments. Neurobiol Dis 22: 346-356.
19. Ratovitski T, Nakamura M, D'Ambola J, Chighladze E, Liang Y, et al. (2007) N-terminal proteolysis of full-length mutant huntingtin in an inducible PC12 cell model of Huntington's disease. Cell Cycle 6: 2970-2981.
20. Ratovitski T, Gucek M, Jiang H, Chighladze E, Waldron E, et al. (2009) Mutant Huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells. J Biol Chem 284: 10855-10867.
21. Wellington CL, Singaraja R, Ellerby L, Savill J, Roy S, et al. (2000) Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J Biol Chem 275: 19831-19838.
22. Wellington CL, Ellerby LM, Gutekunst CA, Rogers D, Warby S, et al. (2002) Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J Neurosci 22: 7862-7872.
23. Gafni J, Hermel E, Young JE, Wellington CL, Hayden MR, et al. (2004) Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus. J Biol Chem 279: 20211-20220.
24. Miller JP, Holcomb J, Al Ramahi I, de Haro M, Gafni J, et al. (2010) Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. Neuron 67: 199-212.
25. Fortun J, Verrier JD, Go JC, Madorsky I, Dunn WA, et al. (2007) The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones. Neurobiol Dis 25: 252-265.
26. Sadasivan S, Waghray A, Larner SF, Dunn WA Jr, Hayes RL, et al. (2006) Amino acid starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1. Apoptosis 11: 1573-1582.
27. Fauq AH, Simpson K, Maharvi GM, Golde T, Das P, (2007) A multigram chemical synthesis of the gamma-secretase inhibitor LY411575 and its diastereoisomers. Bioorg Med Chem Lett 17: 6392-6395.
28. Laemmli UK, (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 227: 680-685.
29. Shaw G, Morse S, Ararat M, Graham FL, (2002) Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells. FASEB J 16: 869-871.
30. Rawlings ND, Barrett AJ, Bateman A, (2010) MEROPS: the peptidase database. Nucleic Acids Res 38: D227-D233.
31. Tompa P, Buzder-Lantos P, Tantos A, Farkas A, Szilagyi A, et al. (2004) On the sequential determinants of calpain cleavage. J Biol Chem 279: 20775-20785.
32. Saido TC, Nagao S, Shiramine M, Tsukaguchi M, Sorimachi H, et al. (1992) Autolytic transition of mu-calpain upon activation as resolved by antibodies distinguishing between the pre- and post-autolysis forms. J Biochem 111: 81-86.
33. Meyer SL, Bozyczko-Coyne D, Mallya SK, Spais CM, Bihovsky R, et al. (1996) Biologically active monomeric and heterodimeric recombinant human calpain I produced using the baculovirus expression system. Biochem J 314 (Pt 2) (): 511-519.
34. Renna M, Jimenez-Sanchez M, Sarkar S, Rubinsztein DC, (2010) Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. J Biol Chem 285: 11061-11067.
35. Mizushima N, (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36: 2491-2502.
36. Yoon YH, Cho KS, Hwang JJ, Lee SJ, Choi JA, et al. (2010) Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells. Invest Ophthalmol Vis Sci 51: 6030-6037.
37. Inagaki R, Tagawa K, Qi ML, Enokido Y, Ito H, et al. (2008) Omi/HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntington's disease. Eur J Neurosci 28: 30-40.
38. Cilenti L, Lee Y, Hess S, Srinivasula S, Park KM, et al. (2003) Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2. J Biol Chem 278: 11489-11494.
39. Goffredo D, Rigamonti D, Zuccato C, Tartari M, Valenza M, et al. (2005) Prevention of cytosolic IAPs degradation: a potential pharmacological target in Huntington's Disease. Pharmacol Res 52: 140-150.
40. Kegel KB, Sapp E, Alexander J, Reeves P, Bleckmann D, et al. (2010) Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors. Mol Neurodegener 5: 58.
41. Lanz TA, Hosley JD, Adams WJ, Merchant KM, (2004) Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575). J Pharmacol Exp Ther 309: 49-55.
42. Lanz TA, Fici GJ, Merchant KM, (2005) Lack of specific amyloid-beta(1-42) suppression by nonsteroidal anti-inflammatory drugs in young, plaque-free Tg2576 mice and in guinea pig neuronal cultures. J Pharmacol Exp Ther 312: 399-406.
43. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, et al. (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391: 387-390.
44. Duckworth WC, Bennett RG, Hamel FG, (1998) Insulin degradation: progress and potential. Endocr Rev 19: 608-624.
45. Edbauer D, Willem M, Lammich S, Steiner H, Haass C, (2002) Insulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD). J Biol Chem 277: 13389-13393.
46. Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, et al. (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100: 4162-4167.
47. Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, et al. (2006) Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 125: 1179-1191.
48. Tebbenkamp AT, Green C, Xu G, Denovan-Wright EM, Rising AC, et al. (2011) Transgenic mice expressing caspase-6-derived N-terminal fragments of mutant huntingtin develop neurologic abnormalities with predominant cytoplasmic inclusion pathology composed largely of a smaller proteolytic derivative. Hum Mol Genet 20: 2770-2782.
49. Dev KK, Chatterjee S, Osinde M, Stauffer D, Morgan H, et al. (2006) Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals. Eur J Pharmacol 540: 10-17.