JOURNAL BROWSE
Search
Advanced SearchSearch Tips
N-Terminal Acetylation-Targeted N-End Rule Proteolytic System: The Ac/N-End Rule Pathway
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Molecules and Cells
  • Volume 39, Issue 3,  2016, pp.169-178
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2329
 Title & Authors
N-Terminal Acetylation-Targeted N-End Rule Proteolytic System: The Ac/N-End Rule Pathway
Lee, Kang-Eun; Heo, Ji-Eun; Kim, Jeong-Mok; Hwang, Cheol-Sang;
  PDF(new window)
 Abstract
Although -terminal acetylation (Nt-acetylation) is a pervasive protein modification in eukaryotes, its general functions in a majority of proteins are poorly understood. In 2010, it was discovered that Nt-acetylation creates a specific protein degradation signal that is targeted by a new class of the N-end rule proteolytic system, called the Ac/N-end rule pathway. Here, we review recent advances in our understanding of the mechanism and biological functions of the Ac/N-end rule pathway, and its crosstalk with the Arg/N-end rule pathway (the classical N-end rule pathway).
 Keywords
degron;N-end rule;N-terminal acetylation;proteolysis;ubiquitin;
 Language
English
 Cited by
1.
Acetylation of N-terminus and two internal amino acids is dispensable for degradation of a protein that aberrantly engages the endoplasmic reticulum translocon, PeerJ, 2017, 5, e3728  crossref(new windwow)
2.
Physiological functions and clinical implications of the N-end rule pathway, Frontiers of Medicine, 2016, 10, 3, 258  crossref(new windwow)
3.
Pro(moting) the Turnover of Gluconeogenic Enzymes by a New Branch of the N-end Rule Pathway, Trends in Biochemical Sciences, 2017, 42, 5, 330  crossref(new windwow)
4.
Life and death of proteins after protease cleavage: protein degradation by the N-end rule pathway, New Phytologist, 2017  crossref(new windwow)
5.
Degradation of SerotoninN-Acetyltransferase, a Circadian Regulator, by the N-end Rule Pathway, Journal of Biological Chemistry, 2016, 291, 33, 17178  crossref(new windwow)
6.
Analyzing N-terminal Arginylation through the Use of Peptide Arrays and Degradation Assays, Journal of Biological Chemistry, 2016, 291, 40, 20976  crossref(new windwow)
7.
From start to finish: amino-terminal protein modifications as degradation signals in plants, New Phytologist, 2016, 211, 4, 1188  crossref(new windwow)
 References
1.
Aksnes, H., Drazic, A., and Arnesen, T. (2015a). (Hyper)tension release by N-terminal acetylation. Trends Biochem. Sci. 40, 422-424. crossref(new window)

2.
Aksnes, H., Hole, K., and Arnesen, T. (2015b). Molecular, cellular, and physiological significance of N-terminal acetylation. Int. Rev. Cell Mol. Biol. 316, 267-305. crossref(new window)

3.
Aksnes, H., Van Damme, P., Goris, M., Starheim, K.K., Marie, M., Stove, S.I., Hoel, C., Kalvik, T.V., Hole, K., Glomnes, N., et al. (2015c). An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity. Cell Rep. 10, 1362-1374. crossref(new window)

4.
Arnesen, T., Van Damme, P., Polevoda, B., Helsens, K., Evjenth, R., Colaert, N., Varhaug, J.E., Vandekerckhove, J., Lillehaug, J.R., Sherman, F., et al. (2009). Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc. Natl. Acad. Sci. USA 106, 8157-8162. crossref(new window)

5.
Arnesen, T., Starheim, K.K., Van Damme, P., Evjenth, R., Dinh, H., Betts, M.J., Ryningen, A., Vandekerckhove, J., Gevaert, K., and Anderson, D. (2010). The chaperone-like protein HYPK acts together with NatA in cotranslational N-terminal acetylation and prevention of Huntingtin aggregation. Mol. Cell. Biol. 30, 1898-1909. crossref(new window)

6.
Bachmair, A., Finley, D., and Varshavsky, A. (1986). In vivo half-life of a protein is a function of its amino-terminal residue. Science 234, 179-186. crossref(new window)

7.
Bagadi, S.A., Prasad, C.P., Srivastava, A., Prashad, R., Gupta, S.D., and Ralhan, R. (2007). Frequent loss of Dab2 protein and infrequent promoter hypermethylation in breast cancer. Breast Cancer Res. Treat. 104, 277-286. crossref(new window)

8.
Behnia, R., Panic, B., Whyte, J.R., and Munro, S. (2004). Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p. Nat. Cell Biol. 6, 405-413. crossref(new window)

9.
Beltran-Alvarez, P., Tarradas, A., Chiva, C., Perez-Serra, A., Batlle, M., Perez-Villa, F., Schulte, U., Sabido, E., Brugada, R., and Pagans, S. (2014). Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart. J. Mol. Cell. Cardiol. 76, 126-129. crossref(new window)

10.
Bhattacharjee, A., Majumdar, U., Maity, D., Sarkar, T.S., Goswami, A.M., Sahoo, R., and Ghosh, S. (2009). In vivo protein tyrosine nitration in S. cerevisiae: identification of tyrosine-nitrated proteins in mitochondria. Biochem. Biophys. Res. Commun. 388, 612-617. crossref(new window)

11.
Bischof, S., Baerenfaller, K., Wildhaber, T., Troesch, R., Vidi, P.A., Roschitzki, B., Hirsch-Hoffmann, M., Hennig, L., Kessler, F., Gruissem, W., et al. (2011). Plastid proteome assembly without Toc159: photosynthetic protein import and accumulation of Nacetylated plastid precursor proteins. Plant Cell 23, 3911-3928. crossref(new window)

12.
Bodenstein, J., Sunahara, R.K., and Neubig, R.R. (2007). Nterminal residues control proteasomal degradation of RGS2, RGS4, and RGS5 in human embryonic kidney 293 cells. Mol. Pharmacol. 71, 1040-1050. crossref(new window)

13.
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., et al. (2015). Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding. Nat. Cell Biol. 17, 917-929. crossref(new window)

14.
Chen, S., Vetro, J.A., and Chang, Y.H. (2002). The specificity in vivo of two distinct methionine aminopeptidases in Saccharomyces cerevisiae. Arch. Biochem. Biophys. 398, 87-93. crossref(new window)

15.
Chen, Y.L., Kuo, M.H., Lin, P.Y., Chuang, W.L., Hsu, C.C., Chu, P.Y., Lee, C.H., Huang, T.H., Leu, Y.W., and Hsiao, S.H. (2013). ENSA expression correlates with attenuated tumor propagation in liver cancer. Biochem. Biophys. Res. Commun. 442, 56-61. crossref(new window)

16.
Ciechanover, A., and Ben-Saadon, R. (2004). N-terminal ubiquitination: more protein substrates join in. Trends Cell Biol. 14, 103-106. crossref(new window)

17.
Ciechanover, A., and Kwon, Y.T. (2015). Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp. Mol. Med. 47, e147. crossref(new window)

18.
Dinh, T.V., Bienvenut, W.V., Linster, E., Feldman-Salit, A., Jung, V.A., Meinnel, T., Hell, R., Giglione, C., and Wirtz, M. (2015). Molecular identification and functional characterization of the first Nalpha-acetyltransferase in plastids by global acetylome profiling. Proteomics 15, 2426-2435. crossref(new window)

19.
Ditzel, M., Wilson, R., Tenev, T., Zachariou, A., Paul, A., Deas, E., and Meier, P. (2003). Degradation of DIAP1 by the N-end rule pathway is essential for regulating apoptosis. Nat. Cell Biol. 5, 467-473. crossref(new window)

20.
Doblas, V.G., Amorim-Silva, V., Pose, D., Rosado, A., Esteban, A., Arro, M., Azevedo, H., Bombarely, A., Borsani, O., Valpuesta, V., et al. (2013). The SUD1 gene encodes a putative E3 ubiquitin ligase and is a positive regulator of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in Arabidopsis. Plant Cell 25, 728-743. crossref(new window)

21.
Dohmen, R.J. (2015). Starting with a degron: N-terminal formylmethionine of nascent bacterial proteins contributes to their proteolytic control. Microbia Cell 2, 356-359. crossref(new window)

22.
Dorfel, M.J., and Lyon, G.J. (2015). The biological functions of Naa10 - From amino-terminal acetylation to human disease. Gene 567, 103-131. crossref(new window)

23.
Dougan, D.A., Micevski, D., and Truscott, K.N. (2012). The N-end rule pathway: from recognition by N-recognins, to destruction by AAA+proteases. Biochim. Biophys. Acta 1823, 83-91. crossref(new window)

24.
Erickson, S.L., Corpuz, E.O., Maloy, J.P., Fillman, C., Webb, K., Bennett, E.J., and Lykke-Andersen, J. (2015). Competition between decapping complex formation and ubiquitin-mediated proteasomal degradation controls human Dcp2 decapping activity. Mol. Cell. Biol. 35, 2144-2153. crossref(new window)

25.
Esmailpour, T., Riazifar, H., Liu, L., Donkervoort, S., Huang, V.H., Madaan, S., Shoucri, B.M., Busch, A., Wu, J., Towbin, A., et al. (2014). A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome. J. Med. Genet. 51, 185-196. crossref(new window)

26.
Ferrandez-Ayela, A., Micol-Ponce, R., Sanchez-Garcia, A.B., Alonso-Peral, M.M., Micol, J.L., and Ponce, M.R. (2013). Mutation of an Arabidopsis NatB N-alpha-terminal acetylation complex component causes pleiotropic developmental defects. PLoS One 8, e80697. crossref(new window)

27.
Foresti, O., Ruggiano, A., Hannibal-Bach, H.K., Ejsing, C.S., and Carvalho, P. (2013). Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4. Elife 2, e00953.

28.
Forte, G.M., Pool, M.R., and Stirling, C.J. (2011). N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum. PLoS Biol. 9, e1001073. crossref(new window)

29.
Garrels, J.I., McLaughlin, C.S., Warner, J.R., Futcher, B., Latter, G.I., Kobayashi, R., Schwender, B., Volpe, T., Anderson, D.S., Mesquita- Fuentes, R., et al. (1997). Proteome studies of Saccharomyces cerevisiae: identification and characterization of abundant proteins. Electrophoresis 18, 1347-1360. crossref(new window)

30.
Gautschi, M., Just, S., Mun, A., Ross, S., Rucknagel, P., Dubaquie, Y., Ehrenhofer-Murray, A., and Rospert, S. (2003). The yeast N(alpha)-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides. Mol. Cell. Biol. 23, 7403-7414. crossref(new window)

31.
Ghislain, M., Dohmen, R.J., Levy, F., and Varshavsky, A. (1996). Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae. EMBO J. 15, 4884-4899.

32.
Gibbs, D.J. (2015). Emerging functions for N-terminal protein acetylation in plants. Trends Plant Sci. 20, 599-601. crossref(new window)

33.
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., et al. (2011). Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants. Nature 479, 415-418. crossref(new window)

34.
Gibbs, D.J., Bacardit, J., Bachmair, A., and Holdsworth, M.J. (2014). The eukaryotic N-end rule pathway: conserved mechanisms and diverse functions. Trends Cell Biol. 24, 603-611. crossref(new window)

35.
Giglione, C., Vallon, O., and Meinnel, T. (2003). Control of protein life-span by N-terminal methionine excision. EMBO J. 22, 13-23. crossref(new window)

36.
Giglione, C., Fieulaine, S., and Meinnel, T. (2015). N-terminal protein modifications: bringing back into play the ribosome. Biochimie 114, 134-146. crossref(new window)

37.
Graveley, B.R., Brooks, A.N., Carlson, J.W., Duff, M.O., Landolin, J.M., Yang, L., Artieri, C.G., van Baren, M.J., Boley, N., Booth, B.W., et al. (2011). The developmental transcriptome of Drosophila melanogaster. Nature 471, 473-479. crossref(new window)

38.
Grimmer, J., Rodiger, A., Hoehenwarter, W., Helm, S., and Baginsky, S. (2014). The RNA-binding protein RNP29 is an unusual Toc159 transport substrate. Front Plant Sci. 5, 258.

39.
Hammerle, M., Bauer, J., Rose, M., Szallies, A., Thumm, M., Dusterhus, S., Mecke, D., Entian, K.D., and Wolf, D.H. (1998). Proteins of newly isolated mutants and the amino-terminal proline are essential for ubiquitin-proteasome-catalyzed catabolite degradation of fructose-1,6-bisphosphatase of Saccharomyces cerevisiae. J. Biol. Chem. 273, 25000-25005. crossref(new window)

40.
Hassink, G., Kikkert, M., van Voorden, S., Lee, S.J., Spaapen, R., van Laar, T., Coleman, C.S., Bartee, E., Fruh, K., Chau, V., et al. (2005). TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum. Biochem. J. 388, 647-655. crossref(new window)

41.
Helbig, A.O., Rosati, S., Pijnappel, P.W., Van Breukelen, B., Timmers, M.H., Mohammed, S., Slijper, M., and Heck, A.J. (2010). Perturbation of the yeast N-acetyltransferase NatB induces elevation of protein phosphorylation levels. BMC Genomics 11, 685. crossref(new window)

42.
Hershko, A., Heller, H., Eytan, E., Kaklij, G., and Rose, I.A. (1984). Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown. Proc. Natl. Acad. Sci. USA 81, 7021-7025. crossref(new window)

43.
Holmes, W.M., Mannakee, B.K., Gutenkunst, R.N., and Serio, T.R. (2014). Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding. Nat. Commun. 5, 4383.

44.
Hu, R.G., Sheng, J., Qi, X., Xu, Z., Takahashi, T.T., and Varshavsky, A. (2005). The N-end rule pathway as a nitric oxide sensor controlling the levels of multiple regulators. Nature 437, 981-986. crossref(new window)

45.
Hwang, C.S., Shemorry, A., Auerbach, D., and Varshavsky, A. (2010a). The N-end rule pathway is mediated by a complex of the RING-type Ubr1 and HECT-type Ufd4 ubiquitin ligases. Nat. Cell Biol. 12, 1177-1185. crossref(new window)

46.
Hwang, C.S., Shemorry, A., and Varshavsky, A. (2010b). N-terminal acetylation of cellular proteins creates specific degradation signals. Science 327, 973-977. crossref(new window)

47.
Hwang, C.S., Sukalo, M., Batygin, O., Addor, M.C., Brunner, H., Aytes, A.P., Mayerle, J., Song, H.K., Varshavsky, A., and Zenker, M. (2011). Ubiquitin ligases of the N-end rule pathway: assessment of mutations in UBR1 that cause the Johanson-Blizzard syndrome. PLoS One 6, e24925. crossref(new window)

48.
Jornvall, H. (1975). Acetylation of Protein N-terminal amino groups structural observations on alpha-amino acetylated proteins. J. Theoretic. Biol. 55, 1-12. crossref(new window)

49.
Kalvik, T.V., and Arnesen, T. (2013). Protein N-terminal acetyltransferases in cancer. Oncogene 32, 269-276. crossref(new window)

50.
Kandoth, C., McLellan, M.D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J.F., Wyczalkowski, M.A., et al. (2013). Mutational landscape and significance across 12 major cancer types. Nature 502, 333-339. crossref(new window)

51.
Khmelinskii, A., and Knop, M. (2014). Analysis of protein dynamics with tandem fluorescent protein timers. Methods Mol. Biol. 1174, 195-210. crossref(new window)

52.
Kim, J.M., and Hwang, C.S. (2014). Crosstalk between the Arg/Nend and Ac/N-end rule. Cell Cycle 13, 1366-1367. crossref(new window)

53.
Kim, I., Miller, C.R., Young, D.L., and Fields, S. (2013). Highthroughput analysis of in vivo protein stability. Mol. Cell Proteomics 12, 3370-3378. crossref(new window)

54.
Kim, H.K., Kim, R.R., Oh, J.H., Cho, H., Varshavsky, A., and Hwang, C.S. (2014). The N-terminal methionine of cellular proteins as a degradation signal. Cell 156, 158-169. crossref(new window)

55.
Kwon, Y.T., Kashina, A.S., and Varshavsky, A. (1999). Alternative splicing results in differential expression, activity, and localization of the two forms of arginyl-tRNA-protein transferase, a component of the N-end rule pathway. Mol. Cell. Biol. 19, 182-193. crossref(new window)

56.
Lee, M.J., Tasaki, T., Moroi, K., An, J.Y., Kimura, S., Davydov, I.V., and Kwon, Y.T. (2005). RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. Proc. Natl. Acad. Sci. USA 102, 15030-15035. crossref(new window)

57.
Lee, K.E., Ahn, J.Y., Kim, J.M., and Hwang, C.S. (2014). Synthetic lethal screen of NAA20, a catalytic subunit gene of NatB Nterminal acetylase in Saccharomyces cerevisiae. J. Microbiol. 52, 842-848. crossref(new window)

58.
Lee, J.H., Jiang, Y., Kwon, Y.T., and Lee, M.J. (2015). Pharmacological modulation of the N-End rule pathway and its therapeutic Implications. Trends Pharmacol. Sci. 36, 782-797. crossref(new window)

59.
Linster, E., Stephan, I., Bienvenut, W.V., Maple-Grodem, J., Myklebust, L.M., Huber, M., Reichelt, M., Sticht, C., Geir Moller, S., Meinnel, T., et al. (2015). Downregulation of N-terminal acetylation triggers ABA-mediated drought responses in Arabidopsis. Nat. Commun. 6, 7640. crossref(new window)

60.
Liu, C.M., Hsieh, C.L., He, Y.C., Lo, S.J., Liang, J.A., Hsieh, T.F., Josson, S., Chung, L.W., Hung, M.C., and Sung, S.Y. (2013). In vivo targeting of ADAM9 gene expression using lentivirusdelivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. PLoS One 8, e53795. crossref(new window)

61.
Lu, Z., and Hunter, T. (2010). Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell Cycle 9, 2342-2352. crossref(new window)

62.
Ma, D.K., Vozdek, R., Bhatla, N., and Horvitz, H.R. (2012). CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-modulated hypoxia-induced behavioral plasticity in C. elegans. Neuron 73, 925-940. crossref(new window)

63.
Malen, H., Lillehaug, J.R., and Arnesen, T. (2009). The protein Nalpha- terminal acetyltransferase hNaa10p (hArd1) is phosphorylated in HEK293 cells. BMC Res Notes 2, 32. crossref(new window)

64.
Meinnel, T., Peynot, P., and Giglione, C. (2005). Processed Ntermini of mature proteins in higher eukaryotes and their major contribution to dynamic proteomics. Biochimie 87, 701-712. crossref(new window)

65.
Menssen, R., Schweiggert, J., Schreiner, J., Kusevic, D., Reuther, J., Braun, B., and Wolf, D.H. (2012). Exploring the topology of the Gid complex, the E3 ubiquitin ligase involved in cataboliteinduced degradation of gluconeogenic enzymes. J. Biol. Chem. 287, 25602-25614. crossref(new window)

66.
Mogk, A., and Bukau, B. (2010). Cell biology. When the beginning marks the end. Science 327, 966-967. crossref(new window)

67.
Mullen, J.R., Kayne, P.S., Moerschell, R.P., Tsunasawa, S., Gribskov, M., Colavito-Shepanski, M., Grunstein, M., Sherman, F., and Sternglanz, R. (1989). Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast. EMBO J. 8, 2067-2075.

68.
Narita, K. (1958). Isolation of acetylpeptide from enzymic digests of TMV-protein. Biochimi. Biophys. Acta 28, 184-191. crossref(new window)

69.
Park, E.C., and Szostak, J.W. (1992). ARD1 and NAT1 proteins form a complex that has N-terminal acetyltransferase activity. EMBO J. 11, 2087-2093.

70.
Park, S.E., Kim, J.M., Seok, O.H., Cho, H., Wadas, B., Kim, S.Y., Varshavsky, A., and Hwang, C.S. (2015). Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway. Science 347, 1249-1252. crossref(new window)

71.
Pena, M.M., Melo, S.P., Xing, Y.Y., White, K., Barbour, K.W., and Berger, F.G. (2009). The intrinsically disordered N-terminal domain of thymidylate synthase targets the enzyme to the ubiquitin- independent proteasomal degradation pathway. J. Biol. Chem. 284, 31597-31607. crossref(new window)

72.
Pesaresi, P., Gardner, N.A., Masiero, S., Dietzmann, A., Eichacker, L., Wickner, R., Salamini, F., and Leister, D. (2003). Cytoplasmic N-terminal protein acetylation is required for efficient photosynthesis in Arabidopsis. Plant Cell 15, 1817-1832. crossref(new window)

73.
Pezza, J.A., Langseth, S.X., Raupp Yamamoto, R., Doris, S.M., Ulin, S.P., Salomon, A.R., and Serio, T.R. (2009). The NatA acetyltransferase couples Sup35 prion complexes to the [PSI+] phenotype. Mol. Biol. Cell 20, 1068-1080.

74.
Piatkov, K.I., Vu, T.M., Hwang, C.S., and Varshavsky, A. (2015). Formyl-methionine as a degradation signal at the N-termini of bacterial proteins. Microbia Cell 2, 376-393. crossref(new window)

75.
Pietrocola, F., Galluzzi, L., Bravo-San Pedro, J.M., Madeo, F., and Kroemer, G. (2015). Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab. 21, 805-821. crossref(new window)

76.
Polevoda, B., Norbeck, J., Takakura, H., Blomberg, A., and Sherman, F. (1999). Identification and specificities of N-terminal acetyltransferases from Saccharomyces cerevisiae. EMBO J. 18, 6155-6168. crossref(new window)

77.
Polevoda, B., Hoskins, J., and Sherman, F. (2009). Properties of Nat4, an N(alpha)-acetyltransferase of Saccharomyces cerevisiae that modifies N termini of histones H2A and H4. Mol. Cell. Biol. 29, 2913-2924. crossref(new window)

78.
Ravid, T., and Hochstrasser, M. (2008). Diversity of degradation signals in the ubiquitin-proteasome system. Nat. Rev. Mol. Cell Biol. 9, 679-690. crossref(new window)

79.
Rope, A.F., Wang, K., Evjenth, R., Xing, J., Johnston, J.J., Swensen, J.J., Johnson, W.E., Moore, B., Huff, C.D., Bird, L.M., et al. (2011). Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency. Am. J. Hum. Genet. 89, 28-43. crossref(new window)

80.
Sawant, S.V., Kiran, K., Singh, P.K., and Tuli, R. (2001). Sequence architecture downstream of the initiator codon enhances gene expression and protein stability in plants. Plant Physiol. 126, 1630-1636. crossref(new window)

81.
Scazzari, M., Amm, I., and Wolf, D.H. (2015). Quality control of a cytoplasmic protein complex: chaperone motors and the ubiquitin- proteasome system govern the fate of orphan fatty acid synthase subunit Fas2 of yeast. J. Biol. Chem. 290, 4677-4687. crossref(new window)

82.
Scott, D.C., Monda, J.K., Bennett, E.J., Harper, J.W., and Schulman, B.A. (2011). N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex. Science 334, 674-678. crossref(new window)

83.
Seo, J.H., Cha, J.H., Park, J.H., Jeong, C.H., Park, Z.Y., Lee, H.S., Oh, S.H., Kang, J.H., Suh, S.W., Kim, K.H., et al. (2010). Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation. Cancer Res. 70, 4422-4432. crossref(new window)

84.
Setty, S.R., Strochlic, T.I., Tong, A.H., Boone, C., and Burd, C.G. (2004). Golgi targeting of ARF-like GTPase Arl3p requires its Nalpha-acetylation and the integral membrane protein Sys1p. Nat. Cell Biol. 6, 414-419. crossref(new window)

85.
Shemorry, A., Hwang, C.S., and Varshavsky, A. (2013). Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Mol. Cell 50, 540-551. crossref(new window)

86.
Silva, R.D., and Martinho, R.G. (2015). Developmental roles of protein N-terminal acetylation. Proteomics 15, 2402-2409. crossref(new window)

87.
Sriram, S.M., Kim, B.Y., and Kwon, Y.T. (2011). The N-end rule pathway: emerging functions and molecular principles of substrate recognition. Nat. Rev. Mol. Cell Biol. 12, 735-747. crossref(new window)

88.
Starheim, K.K., Gevaert, K., and Arnesen, T. (2012). Protein Nterminal acetyltransferases: when the start matters. Trends Biochem. Sci. 37, 152-161. crossref(new window)

89.
Sundberg, T.B., Darricarrere, N., Cirone, P., Li, X., McDonald, L., Mei, X., Westlake, C.J., Slusarski, D.C., Beynon, R.J., and Crews, C.M. (2011). Disruption of Wnt planar cell polarity signaling by aberrant accumulation of the MetAP-2 substrate Rab37. Chem. Biol. 18, 1300-1311. crossref(new window)

90.
Swanson, R., Locher, M., and Hochstrasser, M. (2001). A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation. Genes Dev. 15, 2660-2674. crossref(new window)

91.
Tasaki, T., Sriram, S.M., Park, K.S., and Kwon, Y.T. (2012). The Nend rule pathway. Ann. Rev. Biochem. 81, 261-289. crossref(new window)

92.
Van Damme, P., Hole, K., Pimenta-Marques, A., Helsens, K., Vandekerckhove, J., Martinho, R.G., Gevaert, K., and Arnesen, T. (2011). NatF contributes to an evolutionary shift in protein Nterminal acetylation and is important for normal chromosome segregation. PLoS Genet. 7, e1002169. crossref(new window)

93.
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., et al. (2012). N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. USA 109, 12449-12454. crossref(new window)

94.
Varshavsky, A. (2011). The N-end rule pathway and regulation by proteolysis. Protein Sci. 20, 1298-1345. crossref(new window)

95.
Wang, L., Dong, H., Soroka, C.J., Wei, N., Boyer, J.L., and Hochstrasser, M. (2008). Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II. Hepatology 48, 1558-1569. crossref(new window)

96.
Weits, D.A., Giuntoli, B., Kosmacz, M., Parlanti, S., Hubberten, H.M., Riegler, H., Hoefgen, R., Perata, P., van Dongen, J.T., and Licausi, F. (2014). Plant cysteine oxidases control the oxygendependent branch of the N-end-rule pathway. Nat. Commun. 5, 3425.

97.
Xu, Z., Payoe, R., and Fahlman, R.P. (2012). 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. 287, 7495-7502. crossref(new window)

98.
Xu, F., Huang, Y., Li, L., Gannon, P., Linster, E., Huber, M., Kapos, P., Bienvenut, W., Polevoda, B., Meinnel, T., et al. (2015). Two N-terminal acetyltransferases antagonistically regulate the stability of a nod-like receptor in Arabidopsis. Plant Cell 27, 1547-1562. crossref(new window)

99.
Yamano, K., and Youle, R.J. (2013). PINK1 is degraded through the N-end rule pathway. Autophagy 9, 1758-1769. crossref(new window)