The-N-end rule: The beginning determines the end

Protein and Peptide Letters

Volumn 23, Issue 4, 2016, Pages 343-348

  Eldeeb, Mohamed ^a,b   Fahlman, Richard ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b CAIRO UNIVERSITY   (Egypt)

Author keywords

Degradation signal; N end rule; N terminal acetylation; Proteasome; Protein degradation; Ubiquitin

Indexed keywords

CELL PROTEIN; PROTEASOME; PROTEIN; UBIQUITIN;

AMINO TERMINAL SEQUENCE; ARTICLE; CELL CYCLE; CELL DEATH; CELL DIFFERENTIATION; CELL DIVISION; CELL FUNCTION; CELL PROLIFERATION; ENDOPLASMIC RETICULUM; HUMAN; N END RULE PATHWAY; NONHUMAN; OXIDATIVE STRESS; PROTEIN ACETYLATION; PROTEIN DEGRADATION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; UBIQUITINATION; ANIMAL; CHEMISTRY; METABOLISM; PROTEIN PROCESSING;

ANIMALS; HUMANS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEINS; PROTEOLYSIS; UBIQUITIN; UBIQUITINATION;

EID: 84961757512     PISSN: 09298665     EISSN: 18755305     Source Type: Journal    
DOI: 10.2174/0929866523666160108115809     Document Type: Article

References (62)

1. Varshavsky, A. The ubiquitin system, an immense realm. Annu. Rev. Biochem., 2012, 81, 167-176.
2. Naujokat, C.; Hoffmann, S. Role and function of the 26S proteasome in proliferation and apoptosis. Lab. Invest., 2002, 82, 965-980
3. Pagano, M.; Tam, S. W.; Theodoras, A. M.; Beer-Romano, P.; Del Sal, G.; Chau, V.; Yew, P. R.; Draetta, G. F; Rolfe, M. R. Role of the Ubiquitin-Proteasome pathway in regulating abundance of the CDK inhibitor p27. Science, 1995, 269, 682-685.
4. Buckley, S. M.; Aranda-Orgilles, B.; Strikoudis, A.; Apostolou, E.; Loizou, E.; Moran-Crusio, K.; Farnsworth, C. L.; Koller, A. A.; Dasgupta, R.; Silva, J. C.; Stadtfeld, M.; Hochedlinger, K.; Chen, E. I.; Aifantis I. R. Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system. Cell Stem Cell, 2012, 11, 783-98.
5. Orlowski R. Z. The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ., 1999, 6, 303-313.
6. Piatkov, K. I.; Brower, C. S.; Varshavsky, A. The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments. Proc. Natl. Acad. Sci. USA, 2012, 109, 1839-1847.
7. Eldeeb, M. A.; Fahlman, R. P. The anti-apoptotic form of tyrosine kinase Lyn that is generated by proteolysis is degraded by the N-end rule pathway. Oncotarget, 2014, 5, 2714-22.
8. Ditzel, M.; Wilson, R.; Tenev, T.; Zachariou, A.; Paul, A.; Deas, E.; Meier, P. Degradation of DIAP1 by the N-end rule pathway is essential for regulating apoptosis. Nat. Cell Biol., 2003, 5, 467-473.
9. Varshavsky, A. The N-end rule pathway and regulation by proteolysis. Protein Sci., 2011, 20, 1298-1345.
10. Rogers, S.; Wells, R.; Rechsteiner, M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science, 1986, 234, 364-368.
11. Rechsteiner, M.; Rogers, S. W. PEST sequences and regulation by proteolysis. Trends Biochem. Sci., 1996, 21, 267-271.
12. Campanero, M. R.; Flemington, E. K. Regulation of E2F through ubiquitin-proteasome-dependent degradation: stabilization by the pRB tumor suppressor protein. Proc. Natl. Acad. Sci. USA, 1997, 94, 2221-6.
13. Dohmen, R. J.; Wu, P. P.; Varshavsky, A. Heat-inducible degron: a method for constructing temperature-sensitive mutants. Science, 1994, 263, 1273-1276.
14. Yaglom, J.; Linskens, M. H.; Sadis, S.; Rubin, D. M.; Futcher, B.; Finley, D. p34Cdc28-mediated control of Cln3 cyclin degradation. Mol Cell Biol., 1995, 15, 731-741.
15. Cheng, M.; Olivier, P.; Diehl, J. A.; Fero, M.; Roussel, M. F.; Roberts, J. M.; Sherr, C. J. The p21 (Cip1) and p27 (Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J., 1999, 18, 1571-1583.
16. Freedman, D. A.; Levine, A. J. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol. Cell Biol., 1998, 18, 7288-7293.
17. Tomoda, K.; Kubota, Y.; Kato, J. Degradation of the cyclindependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature, 1999, 398, 160-165.
18. Bachmair, A.; Finley, D.; Varshavsky, A. In vivo half-life of a protein is a function of its N-terminal residue. Science, 1986, 234, 179-186.
19. Tobias, J. W.; Shrader, T. E.; Rocap, G.; Varshavsky, A. The N-end rule in bacteria. Science, 1991, 254, 1374-1377.
20. Gonda, D. K.; Bachmair, A.; Wünning, I.; Tobias, J. W.; Lane, W. S; Varshavsky, A. Universality and structure of the N-end rule. J. Biol. Chem., 1989, 264, 16700-12.
21. Gibbs, D. J.; Lee, S. C.; Isa, N. M.; Gramuglia, S.; Fukao, T.; Bassel, G. W.; Correia, C. S.; Corbineau, F.; Theodoulou, F. L.; Bailey-Serres, J.; Holdsworth, M. J. H. Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants. Nature, 2011, 479, 415-418.
22. Park, S. E.; Kim, J. M.; Seok, O. H.; Cho, H.; Wadas, B.; Kim, S. Y.; Varshavsky, A.; Hwang, C. S. C. Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway, Science, 2015, 347, 1249-1252.
23. Shemorry, A.; Hwang, C. S.; Varshavsky, A. Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Mol. Cell, 2013, 50, 540-51.
24. Rao, H.; Uhlmann, F.; Nasmyth, K.; Varshavsky, A. Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability. Nature, 2001, 410, 955-960.
25. Piatkov, K. I.; Colnaghi, L.; Bekes, M.; Varshavsky, A.; Huang, T. T. The auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway. Mol. Cell, 2012, 48, 926-933.
26. Kwon, Y. T.; Kashina, A. S.; Davydov, I. V.; Hu, R.-G.; An, J. Y.; Seo, J. W.; Du, F.; Varshavsky, A. A. An essential role of N-terminal arginylation in cardiovascular development. Science, 2002, 297, 96-99.
27. Brower, C. S.; Varshavsky, A. Ablation of arginylation in the N-end rule pathway: loss of fat, increased metabolic rate, damaged spermatogenesis, and neurological perturbations. PLoS ONE, 2009, 4, e7757.
28. Turner, G. C.; Du, F.; Varshavsky, A. Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway. Nature, 2000, 405, 579-583.
29. Licausi, F.; Kosmacz, M.; Weits, D. A.; Giuntoli, B.; Giorgi, F. M.; Voesenek, L. A.; Perata, P.; van Dongen, J. T. O. Oxygen sensing in plants is mediated by an N-end rule pathway for protein destabilization. Nature, 2011, 479, 419-22.
30. Dörfel, M. J.; Lyon, G. J. The biological functions of Naa10 - From amino-terminal acetylation to human disease. Gene, 2015, 567, 103-31.
31. Hwang, C-S.; Shemorry, A.; Varshavsky, A. N-terminal acetylation of cellular proteins creates specific degradation signals. Science, 2010, 327, 973-977.
32. Mogk, A.; Bukau, B. Cell biology. When the beginning marks the end. Science, 2010, 327, 966-7.
33. Kim, H. K.; Kim, R. R.; Oh, J. H.; Cho, H.; Varshavsky, A.; Hwang, C. S. The N-terminal methionine of cellular proteins as a degradation signal. Cell, 2014, 156, 158-69.
34. Shemorry, A.; Hwang, C-S.; Varshavsky, A. Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Mol. Cell, 2013, 50, 540-551.
35. Aksnes, H.; Drazic, A.; Arnesen, T. (Hyper) tension release by N-terminal acetylation. Trends Biochem. Sci., 2015, 40, 422-4.
36. Lee, J. H.; Jiang, Y.; Kwon, Y. T.; Lee, M. J. Pharmacological Modulation of the N-End Rule Pathway and its Therapeutic Implications. Trends Pharmacol. Sci., 2015, 36, 782-97.3
37. Xu, Z.; Payoe, R.; Fahlman, R. P. The C-terminal proteolytic fragment of the breast cancer susceptibility type 1 protein (BRCA1) is degraded by the N-end rule pathway. J. Biol. Chem., 2012, 287, 7495-7502.
38. Aksnes, H.; Hole, K.; Arnesen, T. Molecular, Cellular, and Physiological Significance of N-Terminal Acetylation. Int. Rev. Cell Mol. Biol., 2015, 316, 267-305.
39. Holmes, W. M.; Mannakee, B. K.; Gutenkunst, R. N.; Serio, T. R. Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding. Nat. Commun., 2014, 5, 1-11.
40. Sriram, S.; Lee, J. H.; Mai, B. K.; Jiang, Y.; Kim, Y.; Yoo, Y. D.; Banerjee, R.; Lee, S. H.; Lee, M. J. D. Development and Characterization of Monomeric N-End Rule Inhibitors through In Vitro Model Substrates J. Med. Chem., 2013, 56, 2540-2546.
41. Miller, V. J.; Ungar, D. Re'COG'nition at the Golgi. Traffic, 2012, 13, 891-897.
42. Sztul, E.; Lupashin, V. Role of vesicle tethering factors in the ER-Golgi membrane traffic. FEBS Lett., 2009, 583, 3770-3783.
43. Arnesen, T.; Van, Damme, P.; Polevoda, B.; Helsens, K.; Evjenth, R.; Colaert, N.; Varhaug, J. E.; Vandekerckhove, J.; Lillehaug, J. R.; Sherman, F.; Gevaert, K. P. Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc. Natl. Acad. Sci. USA., 2009, 106, 8157-8162.
44. Van Damme, P.; Lasa, M.; Polevoda, B.; Gazquez, C.; Elosegui-Artola, A.; Kim, D. S.; De Juan-Pardo, E.; Demeyer, K.; Hole, K.; Larrea, E.; Timmerman, E.; Prieto, J.; Arnesen, T.; Sherman, F.; Gevaert, K.; Aldabe, R. N. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. USA, 2012, 109, 12449-12454.
45. Piatkov, K. I.; Colnaghi, L.; Bekes, M.; Varshavsky, A.; Huang, TT. The auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway. Mol. Cell, 2012, 48, 926-933.
46. Lee, J. H.; Jiang, Y.; Kwon, Y. T.; Lee, M. J. Pharmacological Modulation of the N-End Rule Pathway and Its Therapeutic Implications. Trends Pharmacol. Sci., 2015, 36, 782-789.
47. Rong-Gui, H.u.; Haiqing, W.; Zanxian X.; Alexander, V. The N-end rule pathway is a sensor of heme. Proc. Natl. Acad. Sci., 2007, 105, 76-81.
48. Yamano, K.; Youle, R. J. PINK1 is degraded through the N-end rule pathway. Autophagy, 2013, 9, 1758-1769.
49. Cha-Molstad, H.; Sung, K. S.; Hwang, J.; Kim, K. A.; Yu, J. E.; Yoo, Y. D.; Jang, J. M.; Han, D. H.; Molstad, M.; Kim, J. G.; Lee, Y. J.; Zakrzewska, A.; Kim, S. H.; Kim, S. T.; Kim, S. Y.; Lee, H. G.; Soung, N. K.; Ahn, J. S.; Ciechanover, A.; Kim, B. Y.; Kwon, Y. T. A. Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding. Nat. Cell Biol., 2015, 17, 917-929.
50. Zenker, M.; Mayerle, J.; Lerch, M. M.; Tagariello, A.; Zerres, K.; Durie, P. R.; Beier, M.; Hülskamp, G.; Guzman, C.; Rehder, H.; Beemer, F. A.; Hamel, B.; Vanlieferinghen, P.; Gershoni-Baruch, R.; Vieira, M. W.; Dumic, M.; Auslender, R.; Gil-Da-Silva-Lopes, V. L.; Steinlicht, S.; Rauh, M.; Shalev, S. A.; Thiel, C.; Ekici, A. B.; Winterpacht, A.; Kwon, Y. T.; Varshavsky, A.; Reis, A. D. Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). Nat. Genet., 2005, 37, 1345-1350.
51. Clancy, J. L.; Henderson, M. J.; Russell, A. J.; Anderson, D. W.; Bova, R. J.; Campbell, I. G.; Choong, D. Y.; Macdonald, G. A.; Mann, G. J.; Nolan, T.; Brady, G.; Olopade, O. I.; Woollatt, E.; Davies, M. J. S. Segara, D.; Hacker, N. F.; Henshall, S. M.; Sutherland, R. L.; Watts, C. K. EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene, 2003, 22, 5070-5081.
52. Fuja, T. J.; Lin, F.; Osann, K. E.; Bryant, P. J. Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma. Cancer Res., 2004, 64, 942-951.
53. O'Brien, P. M.; Davies, M. J.; Scurry, J. P.; Smith, A. N.; Barton, C. A.; Henderson, M. J.; Saunders, D. N.; Gloss, B. S.; Patterson, K. I.; Clancy, J. L.; Heinzelmann-Schwarz, V. A.; Murali, R.; Scolyer, R. A.; Zeng, Y.; Williams, E. D.; Scurr, L.; Defazio, A.; Quinn, D. I.; Watts, C. K.; Hacker, N. F.; Henshall, S. M.; Sutherland, R. L. T. The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro. Br. J. Cancer, 2008, 98, 1085-1093.
54. Adibhatla, R. M.; Hatcher, J. F. Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox. Signal., 2010, 12, 125-169.
55. Bochkov, VN.; Oskolkova, OV.; Birukov, KG.; Levonen, AL.; Binder, CJ.; Stöckl, J. Generation and biological activities of oxidized phospholipids. Antioxid Redox Signal., 2010, 12, 1009-1059.
56. Sedelnikova, OA.; Redon, CE.; Dickey, JS.; Nakamura, AJ.; Georgakilas, AG.; Bonner, WM. Role of oxidatively induced DNA lesions in human pathogenesis. Mutat. Res., 2010, 704, 152-159.
57. Uttara, B.; Singh, A. V.; Zamboni, P.; Mahajan, R. T. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7, 65-74.
58. Stadtman, E. R. Protein oxidation and aging. Free Radic. Res., 2006, 40, 1250-1258.
59. Ahmed, E. K.; Picot, C. R.; Bulteau, A. L.; Friguet, B. Protein oxidative modifications and replicative senescence of WI-38 human embryonic fibroblasts. Ann. NY. Acad. Sci., 2007, 1119, 88-96.
60. Brower, C. S.; Piatkov, K. I.; Varshavsky, A. Neurodegenerationassociated protein fragments as short-lived substrates of the N-end rule pathway. Mol. Cell, 2013, 50, 161-171.
61. David, D. C.; Layfield, R.; Serpell, L.; Narain, Y.; Goedert, M.; Spillantini, M. G. Proteasomal degradation of tau protein. J. Neurochem., 2002, 83, 176-185.
62. Lange, P. F.; Huesgen, P. F.; Nguyen, K.; Overall, C. M. Annotating N termini for the human proteome project: N termini and Nalphaacetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J. Proteome Res., 2014, 13, 2028-2044.