Skip to main content
SpringerLink
Log in

Protein Arginylation: Over 50 Years of Discovery

  • Protocol
Book cover Protein Arginylation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1337))

Abstract

Posttranslational modifications have emerged in recent years as the major biological regulators responsible for the orders of magnitude increase in complexity of protein functions. These “molecular switches” affect nearly every protein in vivo by modulating their protein structure, activity, molecular interactions, and homeostasis. While over 350 protein modifications have been described, only a handful of them have been characterized. Until recently, protein arginylation has belonged to the list of obscure, poorly understood posttranslational modifications, before the recent explosion of studies has put arginylation on the map of intracellular metabolic pathways and biological processes. This chapter contains an overview of all the major milestones in the protein arginylation field, from its original discovery in 1963 to this day.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kaji A, Kaji H, Novelli GD (1963) A soluble amino acid incorporating system. Biochem Biophys Res Commun 10:406–409

    Article  CAS  PubMed  Google Scholar 

  2. Kaji A, Kaji H, Novelli GD (1965) Soluble amino acid-incorporating system. II. Soluble nature of the system and the characterization of the radioactive product. J Biol Chem 240:1192–1197

    CAS  PubMed  Google Scholar 

  3. Kaji A, Kaji H, Novelli GD (1965) Soluble amino acid-incorporating system. I. Preparation of the system and nature of the reaction. J Biol Chem 240:1185–1191

    CAS  PubMed  Google Scholar 

  4. Momose K, Kaji A (1966) Soluble amino acid-incorporating system. 3. Further studies on the product and its relation to the ribosomal system for incorporation. J Biol Chem 241(14):3294–3307

    CAS  PubMed  Google Scholar 

  5. Kaji H, Novelli GD, Kaji A (1963) A soluble amino acid-incorporating system from rat liver. Biochim Biophys Acta 76:474–477

    Article  CAS  PubMed  Google Scholar 

  6. Kaji H (1968) Further studies on the soluble amino acid incorporating system from rat liver. Biochemistry 7(11):3844–3850

    Article  CAS  PubMed  Google Scholar 

  7. Kaji H, Rao P (1976) Membrane modification by arginyl tRNA. FEBS Lett 66(2):194–197

    Article  CAS  PubMed  Google Scholar 

  8. Manahan CO, App AA (1973) An arginyl-transfer ribonucleic acid protein transferase from cereal embryos. Plant Physiol 52(1):13–16

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Lock RA, Harding HW, Rogers GE (1976) Arginine transferase activity in homogenates from guinea-pig hair follicles. J Invest Dermatol 67(5):582–586

    Article  CAS  PubMed  Google Scholar 

  10. Lamon KD, Kaji H (1980) Arginyl-tRNA transferase activity as a marker of cellular aging in peripheral rat tissues. Exp Gerontol 15(1):53–64

    Article  CAS  PubMed  Google Scholar 

  11. Wang YM, Ingoglia NA (1997) N-terminal arginylation of sciatic nerve and brain proteins following injury. Neurochem Res 22(12):1453–1459

    Article  CAS  PubMed  Google Scholar 

  12. Xu NS, Chakraborty G, Hassankhani A, Ingoglia NA (1993) N-terminal arginylation of proteins in explants of injured sciatic nerves and embryonic brains of rats. Neurochem Res 18(11):1117–1123

    Article  CAS  PubMed  Google Scholar 

  13. Zhang N, Donnelly R, Ingoglia NA (1998) Evidence that oxidized proteins are substrates for N-terminal arginylation. Neurochem Res 23(11):1411–1420

    Article  CAS  PubMed  Google Scholar 

  14. Ciechanover A, Ferber S, Ganoth D, Elias S, Hershko A, Arfin S (1988) Purification and characterization of arginyl-tRNA-protein transferase from rabbit reticulocytes. Its involvement in post-translational modification and degradation of acidic NH2 termini substrates of the ubiquitin pathway. J Biol Chem 263(23):11155–11167

    CAS  PubMed  Google Scholar 

  15. Balzi E, Choder M, Chen WN, Varshavsky A, Goffeau A (1990) Cloning and functional analysis of the arginyl-tRNA-protein transferase gene ATE1 of Saccharomyces cerevisiae. J Biol Chem 265(13):7464–7471

    CAS  PubMed  Google Scholar 

  16. Kaji H (1976) Amino-terminal arginylation of chromosomal proteins by arginyl-tRNA. Biochemistry 15(23):5121–5125

    Article  CAS  PubMed  Google Scholar 

  17. Bohley P, Kopitz J, Adam G, Rist B, von Appen F, Urban S (1991) Post-translational arginylation and intracellular proteolysis. Biomed Biochim Acta 50(4-6):343–346

    CAS  PubMed  Google Scholar 

  18. Hallak ME, Barra HS, Caputto R (1985) Posttranslational incorporation of [14C]arginine into rat brain proteins. Acceptor changes during development. J Neurochem 44(3):665–669

    Article  CAS  PubMed  Google Scholar 

  19. Takao K, Samejima K (1999) Arginyl-tRNA-protein transferase activities in crude supernatants of rat tissues. Biol Pharm Bull 22(9):1007–1009

    Article  CAS  PubMed  Google Scholar 

  20. Hallak ME, Bongiovanni G, Barra HS (1991) The posttranslational arginylation of proteins in different regions of the rat brain. J Neurochem 57(5):1735–1739

    Article  CAS  PubMed  Google Scholar 

  21. Wagner BJ, Margolis JW (1991) Post-translational arginylation in the bovine lens. Exp Eye Res 53(5):609–614

    Article  CAS  PubMed  Google Scholar 

  22. Fissolo S, Bongiovanni G, Decca MB, Hallak ME (2000) Post-translational arginylation of proteins in cultured cells. Neurochem Res 25(1):71–76

    Article  CAS  PubMed  Google Scholar 

  23. Rao P, Kaji H (1977) Comparative studies on isoaccepting arginyl tRNAs from transformed cells and their utilization in post-translational protein modification. Arch Biochem Biophys 181(2):591–595

    Article  CAS  PubMed  Google Scholar 

  24. Kopitz J, Rist B, Bohley P (1990) Post-translational arginylation of ornithine decarboxylase from rat hepatocytes. Biochem J 267(2):343–348

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Bohley P, Kopitz J, Adam G (1988) Surface hydrophobicity, arginylation and degradation of cytosol proteins from rat hepatocytes. Biol Chem Hoppe Seyler 369(Suppl):307–310

    CAS  PubMed  Google Scholar 

  26. Bohley P, Kopitz J, Adam G (1988) Arginylation, surface hydrophobicity and degradation of cytosol proteins from rat hepatocytes. Adv Exp Med Biol 240:159–169

    Article  CAS  PubMed  Google Scholar 

  27. Soffer RL (1971) Enzymatic modification of proteins. 4. Arginylation of bovine thyroglobulin. J Biol Chem 246(5):1481–1484

    CAS  PubMed  Google Scholar 

  28. Eriste E, Norberg A, Nepomuceno D, Kuei C, Kamme F, Tran DT, Strupat K, Jornvall H, Liu C, Lovenberg TW, Sillard R (2005) A novel form of neurotensin post-translationally modified by arginylation. J Biol Chem 280(42):35089–35097

    Article  CAS  PubMed  Google Scholar 

  29. Soffer RL (1975) Enzymatic arginylation of beta-melanocyte-stimulating hormone and of angiotensin II. J Biol Chem 250(7):2626–2629

    CAS  PubMed  Google Scholar 

  30. Bachmair A, Finley D, Varshavsky A (1986) In vivo half-life of a protein is a function of its amino-terminal residue. Science 234(4773):179–186

    Article  CAS  PubMed  Google Scholar 

  31. Gonda DK, Bachmair A, Wunning I, Tobias JW, Lane WS, Varshavsky A (1989) Universality and structure of the N-end rule. J Biol Chem 264(28):16700–16712

    CAS  PubMed  Google Scholar 

  32. Varshavsky A (1992) The N-end rule. Cell 69(5):725–735

    Article  CAS  PubMed  Google Scholar 

  33. Varshavsky A (1995) The N-end rule. Cold Spring Harb Symp Quant Biol 60:461–478

    Article  CAS  PubMed  Google Scholar 

  34. Elias S, Ciechanover A (1990) Post-translational addition of an arginine moiety to acidic NH2 termini of proteins is required for their recognition by ubiquitin-protein ligase. J Biol Chem 265(26):15511–15517

    CAS  PubMed  Google Scholar 

  35. Davydov IV, Varshavsky A (2000) RGS4 is arginylated and degraded by the N-end rule pathway in vitro. J Biol Chem 275(30):22931–22941

    Article  CAS  PubMed  Google Scholar 

  36. Lee MJ, Tasaki T, Moroi K, An JY, Kimura S, Davydov IV, Kwon YT (2005) RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. Proc Natl Acad Sci U S A 102(42):15030–15035

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Kwon YT, Kashina AS, 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(1):182–193

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Rai R, Kashina A (2005) Identification of mammalian arginyltransferases that modify a specific subset of protein substrates. Proc Natl Acad Sci U S A 102(29):10123–10128

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Hu RG, Brower CS, Wang H, Davydov IV, Sheng J, Zhou J, Kwon YT, Varshavsky A (2006) Arginyltransferase, its specificity, putative substrates, bidirectional promoter, and splicing-derived isoforms. J Biol Chem 281(43):32559–32573

    Article  CAS  PubMed  Google Scholar 

  40. Kwon YT, Kashina AS, Davydov IV, Hu RG, An JY, Seo JW, Du F, Varshavsky A (2002) An essential role of N-terminal arginylation in cardiovascular development. Science 297(5578):96–99

    Article  CAS  PubMed  Google Scholar 

  41. Kurosaka S, Leu NA, Zhang F, Bunte R, Saha S, Wang J, Guo C, He W, Kashina A (2010) Arginylation-dependent neural crest cell migration is essential for mouse development. PLoS Genet 6(3):e1000878

    Article  PubMed Central  PubMed  Google Scholar 

  42. Rai R, Wong CC, Xu T, Leu NA, Dong DW, Guo C, McLaughlin KJ, Yates JR 3rd, Kashina A (2008) Arginyltransferase regulates alpha cardiac actin function, myofibril formation and contractility during heart development. Development 135(23):3881–3889

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Leu NA, Kurosaka S, Kashina A (2009) Conditional Tek promoter-driven deletion of arginyltransferase in the germ line causes defects in gametogenesis and early embryonic lethality in mice. PLoS One 4(11):e7734

    Article  PubMed Central  PubMed  Google Scholar 

  44. Brower CS, Varshavsky A (2009) Ablation of arginylation in the mouse N-end rule pathway: loss of fat, higher metabolic rate, damaged spermatogenesis, and neurological perturbations. PLoS One 4(11):e7757

    Article  PubMed Central  PubMed  Google Scholar 

  45. Yoshida S, Ito M, Callis J, Nishida I, Watanabe A (2002) A delayed leaf senescence mutant is defective in arginyl-tRNA:protein arginyltransferase, a component of the N-end rule pathway in Arabidopsis. Plant J 32(1):129–137

    Article  CAS  PubMed  Google Scholar 

  46. Lim PO, Kim HJ, Nam HG (2007) Leaf senescence. Annu Rev Plant Biol 58:115–136

    Article  CAS  PubMed  Google Scholar 

  47. Graciet E, Walter F, Maoileidigh DO, Pollmann S, Meyerowitz EM, Varshavsky A, Wellmer F (2009) The N-end rule pathway controls multiple functions during Arabidopsis shoot and leaf development. Proc Natl Acad Sci U S A 106(32):13618–13623

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Holman TJ, Jones PD, Russell L, Medhurst A, Ubeda Tomas S, Talloji P, Marquez J, Schmuths H, Tung SA, Taylor I, Footitt S, Bachmair A, Theodoulou FL, Holdsworth MJ (2009) The N-end rule pathway promotes seed germination and establishment through removal of ABA sensitivity in Arabidopsis. Proc Natl Acad Sci U S A 106(11):4549–4554

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Saha S, Kashina A (2011) Posttranslational arginylation as a global biological regulator. Dev Biol 358(1):1–8

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Wong CCL, Xu T, Rai R, Bailey AO, Yates JR, Wolf YI, Zebroski H, Kashina A (2007) Global analysis of posttranslational protein arginylation. PLoS Biol 5(10), e258

    Article  PubMed Central  PubMed  Google Scholar 

  51. Xu T, Wong CCL, Kashina A, Yates JR III (2009) Identification of posstranslationally arginylated proteins and peptides by mass spectrometry. Nat Protoc 43(3):325–332

    Article  Google Scholar 

  52. Saha S, Wong CC, Xu T, Namgoong S, Zebroski H, Yates JR 3rd, Kashina A (2011) Arginylation and methylation double up to regulate nuclear proteins and nuclear architecture in vivo. Chem Biol 18(11):1369–1378

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Karakozova M, Kozak M, Wong CC, Bailey AO, Yates JR 3rd, Mogilner A, Zebroski H, Kashina A (2006) Arginylation of beta-actin regulates actin cytoskeleton and cell motility. Science 313(5784):192–196

    Article  CAS  PubMed  Google Scholar 

  54. Saha S, Mundia MM, Zhang F, Demers RW, Korobova F, Svitkina T, Perieteanu AA, Dawson JF, Kashina A (2010) Arginylation regulates intracellular actin polymer level by modulating actin properties and binding of capping and severing proteins. Mol Biol Cell 21(8):1350–1361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Carpio MA, Decca MB, Lopez Sambrooks C, Durand ES, Montich GG, Hallak ME (2013) Calreticulin-dimerization induced by post-translational arginylation is critical for stress granules scaffolding. Int J Biochem Cell Biol 45(7):1223–1235

    Article  CAS  PubMed  Google Scholar 

  56. Lopez Sambrooks C, Carpio MA, Hallak ME (2012) Arginylated calreticulin at plasma membrane increases susceptibility of cells to apoptosis. J Biol Chem 287(26):22043–22054

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Carpio MA, Lopez Sambrooks C, Durand ES, Hallak ME (2010) The arginylation-dependent association of calreticulin with stress granules is regulated by calcium. Biochem J 429(1):63–72

    Article  CAS  PubMed  Google Scholar 

  58. Decca MB, Carpio MA, Bosc C, Galiano MR, Job D, Andrieux A, Hallak ME (2007) Post-translational arginylation of calreticulin: a new isospecies of calreticulin component of stress granules. J Biol Chem 282(11):8237–8245

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Zhang F, Saha S, Kashina A (2012) Arginylation-dependent regulation of a proteolytic product of talin is essential for cell-cell adhesion. J Cell Biol 197(6):819–836

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Lian L, Suzuki A, Hayes V, Saha S, Han X, Xu T, Yates JR, Poncz M, Kashina A, Abrams CS (2014) Loss of ATE1-mediated arginylation leads to impaired platelet myosin phosphorylation, clot retraction, and in vivo thrombosis formation. Haematologica 99:554

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Cornachione AS, Leite FS, Wang J, Leu NA, Kalganov A, Volgin D, Han X, Xu T, Cheng YS, Yates JR 3rd, Rassier DE, Kashina A (2014) Arginylation of myosin heavy chain regulates skeletal muscle strength. Cell Rep 8:470

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Zhang F, Saha S, Shabalina SA, Kashina A (2010) Differential arginylation of actin isoforms is regulated by coding sequence-dependent degradation. Science 329(5998):1534–1537

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA, 19104, USA

    Anna S. Kashina

Authors
  1. Anna S. Kashina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna S. Kashina .

Editor information

Editors and Affiliations

  1. Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA

    Anna S. Kashina

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Kashina, A.S. (2015). Protein Arginylation: Over 50 Years of Discovery. In: Kashina, A. (eds) Protein Arginylation. Methods in Molecular Biology, vol 1337. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2935-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2935-1_1

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2934-4

  • Online ISBN: 978-1-4939-2935-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation