Abstract
All eukaryotic cells contain enzymes that are able to catalyze the transfer of Arg from tRNA to the N-terminus of naturally short lived or damaged cytosolic proteins. For certain test proteins, it has been shown that the addition of Arg to the N-terminus leads to their degradation via the ubiquitin proteolytic pathway. The mechanisms used by cells for identifying proteins for arginylation and regulating arginylation are not known. The present study reports the isolation of a peptide from rat brain that is able to inhibit the arginylation of proteins in brain extracts. We suggest that this peptide is the physiological regulator of arginylation in rat brain.
Similar content being viewed by others
References
Bachmair A., Finley D., and Varshavsky A. (1986) In vivo half life of a protein is a function of its aminoterminal residue.Science 234, 179–234.
Balzi E., Choder M., Chen W., Varshavsky A., and Goffeau A. (1990) Cloning and functional analysis of the arginyl-tRNA-protein transferase gene ATE1 of Saccharomyces cerevisiae.J. Biol. Chem. 265, 7464–7471.
Barra H. S., Rodriguez J. A., Arce C. A., and Caputto, R. (1973) A soluble preparation from rat brain that incorporates into its own proteins [14C] arginine by an RNase-sensitive system and [14C] tyrosine by an RNase-insensitive system.J. Neurochem. 20, 97–105.
Bradford M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding.Anal. Biochem. 72, 248–254.
Chakraborty G., and Nngoglia N. A. (1993) N-terminal arginylation and ubiquitin mediated proteolysis in nerve regeneration.Brain Res. Bull. 30, 439–445.
Chakraborty G, Nicola A., and Ingoglia N. A. (1992) Evidence that axonal tRNAs are resistant to RNase and ATPase and can be aminoacylated in the absence of exogenous ATP.J. Neurochem. 59, 273–281.
Chakraborty G., Sturman J.A., and Ingoglia N. A. (1990a) Regulation of the posttranslational conjugation of arginine and lysine to rat brain proteins.Neuroscience 37, 215–221.
Chakraborty G, Yu M., Luo D., Sturman J. A., and Ingoglia N. A. (1990b) Amino acid modification of proteins in regenerating sciatic nerves of rat.J. Neurosci. Res. 25, 503–510.
Elias S. and 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, 15,511–15,517.
Ferber S. and Ciechanover A. (1987) Role of arginine tRNA in protein degradation by the ubiquitin pathway.Nature (Lond.)326, 808–811.
Hershko A. and Ciechanover A. (1992) The ubiquitin system for protein degradation.Ann. Rev. Biochem. 61, 761–807.
Ingoglia N. A., Giuditta A., Zanakis M. F., Babigian A., Tasaki I., Chakraborty G., and Sturman J. (1983) Incorporation of3H-amino acids into proteins in a partially purified fraction of axoplasm: evidence for transfer RNA mediated, posttranslational protein modification in squid giant axons.J. Neurosci. 3(12), 2463–2473.
Jack D., Chakraborty G., and Ingoglia N. A. (1992) Ubiquitin is associated with aggregates of arginine modified proteins in injured nerves.NeuroReport 3, 47–50.
Johnson E. S., Bartel B., Seufert W., and Varshavsky, A. (1992) Ubiquitin as a degradation signal.EMBO J. 11, 497–505.
Schacterle G. R. and Pollack R. L. (1973) A simplified method for the quantitative assay of small amounts of protein in biological materials.Anal. Biochem. 51, 654–655.
Sedmak J. J. and Grossberg S. E. (1977) A rapid, sensitive and versatile assay for protein using Coomassie Brilliant Blue G250.Anal. Biochem. 79, 544–552.
Shyne-Athwal S., Chakraborty G., Gage E., and Ingoglia N. A. (1988) Comparison of posttranslational protein modification by amino acid addition after crush injury to sciatic and optic nerves of rats.Exper. Neurol. 99, 281–285.
Shyne-Athwal S., Riccio R., Chakraborty G., and Ingoglia N. A. (1986) Protein modification by amino acid addition is increased in crushed sciatic but not optic nerves.Science 231, 603–605.
Soffer R. L. (1980) Biochemistry and biology of amino acyl tRNA protein transferases, inTransfer RNA: Biological Aspects (Soll D., Abelson J. N. and Schimmel P. R., eds.) Monograph No. 93, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 493–505.
Zanakis M. F., Chakraborty G, Sturman J. A., and Ingoglia, N. A. (1984) Posttranslational protein modification by amino acid addition in intact and regenerating axons of the rat sciatic nerve.J. Neurochem. 43, 1286–1294.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yu, M., Grabow, M. & Ingoglia, N.A. Isolation of a peptide that inhibits the posttranslational arginylation of proteins in rat brain. J Mol Neurosci 4, 195–203 (1993). https://doi.org/10.1007/BF02782502
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02782502