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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 Dec;70(12 Pt 1-2):3866–3869. doi: 10.1073/pnas.70.12.3866

Mechanism of Puromycin Action: Fate of Ribosomes after Release of Nascent Protein Chains from Polysomes

M E Azzam 1,2, I D Algranati 1,2
PMCID: PMC427346  PMID: 4590173

Abstract

The exchange of ribosomal subunits during the release of growing polypeptide chains by puromycin has been investigated in a bacterial cell-free system engaged in protein synthesis. The addition of spermidine, used as a stabilizing agent of 70S monomers, caused a strong inhibition of the subunit exchange. This result led us to conclude that upon premature release of unfinished protein chains by the antibiotic, the ribosomes fall off mRNA as 70S particles. This behavior is different from that occurring during physiological termination of translation, where the ribosomes detach in a dissociated form. Some implications of the postulated mechanism are also discussed.

Keywords: subunit exchange, spermidine, protein synthesis, ribosome cycle

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALLEN D. W., ZAMECNIK P. C. The effect of puromycin on rabbit reticulocyte ribosomes. Biochim Biophys Acta. 1962 Jun 11;55:865–874. doi: 10.1016/0006-3002(62)90899-5. [DOI] [PubMed] [Google Scholar]
  2. Azzam M. E., Perazzolo C. A., Algranati I. D. Polypeptide synthesis in Escherichia coli extracts: Effect of spermidine on the exchange of ribosomal subunits. FEBS Lett. 1972 Mar 15;21(2):165–168. doi: 10.1016/0014-5793(72)80128-5. [DOI] [PubMed] [Google Scholar]
  3. Kaempfer R., Meselson M. Studies of ribosomal subunit exchange. Cold Spring Harb Symp Quant Biol. 1969;34:209–220. doi: 10.1101/sqb.1969.034.01.027. [DOI] [PubMed] [Google Scholar]
  4. Kohler R. E., Ron E. Z., Davis B. D. Significance of the free 70 s ribosomes in Escherichia coli extracts. J Mol Biol. 1968 Aug 28;36(1):71–82. doi: 10.1016/0022-2836(68)90220-9. [DOI] [PubMed] [Google Scholar]
  5. NATHANS D. PUROMYCIN INHIBITION OF PROTEIN SYNTHESIS: INCORPORATION OF PUROMYCIN INTO PEPTIDE CHAINS. Proc Natl Acad Sci U S A. 1964 Apr;51:585–592. doi: 10.1073/pnas.51.4.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Perazzolo C. A., Azzam M. E., Algranati I. D. Termination of polypeptide synthesis in bacteria and the exchange of ribosomal subunits. Eur J Biochem. 1973 May 2;34(3):467–473. doi: 10.1111/j.1432-1033.1973.tb02781.x. [DOI] [PubMed] [Google Scholar]
  7. Pestka S., Hintikka H. Studies on the formation of ribonucleic acid-ribosome complexes. XVI. Effect of ribosomal translocation inhibitors on polyribosomes. J Biol Chem. 1971 Dec 25;246(24):7723–7730. [PubMed] [Google Scholar]
  8. Pestka S. Inhibitors of ribosome functions. Annu Rev Microbiol. 1971;25:487–562. doi: 10.1146/annurev.mi.25.100171.002415. [DOI] [PubMed] [Google Scholar]
  9. Pestka S. Studies on transfer ribonucleic acid-ribosome complexes. XIX. Effect of antibiotics on peptidyl puromycin synthesis on polyribosoms from Escherichia coli. J Biol Chem. 1972 Jul 25;247(14):4669–4678. [PubMed] [Google Scholar]
  10. RABINOVITZ M., FISHER J. M. A dissociative effect of puromycin on the pathway of protein synthesis by Ehrlich ascites tumor cells. J Biol Chem. 1962 Feb;237:477–481. [PubMed] [Google Scholar]
  11. Ron E. Z., Kohler R. E., Davis B. D. Increased stability of polysomes in an Escherichia coli mutant with relaxed control of RNA synthesis. Proc Natl Acad Sci U S A. 1966 Aug;56(2):471–475. doi: 10.1073/pnas.56.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ron E. Z., Kohler R. E., Davis B. D. Magnesium ion dependence of free and polysomal ribosomes from Escherichia coli. J Mol Biol. 1968 Aug 28;36(1):83–89. doi: 10.1016/0022-2836(68)90221-0. [DOI] [PubMed] [Google Scholar]
  13. Schlessinger D., Mangiarotti G., Apirion D. The formation and stabilization of 30S and 50S ribosome couples in Escherichia coli. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1782–1789. doi: 10.1073/pnas.58.4.1782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Subramanian A. R., Davis B. D. Rapid exchange of subunits between free ribosomes in extracts of Escherichia coli. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2453–2457. doi: 10.1073/pnas.68.10.2453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. VILLA-TREVINO S., FARBER E., STAEHELIN T., WETTSTEIN F. O., NOLL H. BREAKDOWN AND REASSEMBLY OF RAT LIVER ERGOSOMES AFTER ADMINISTRATION OF ETHIONINE OR PUROMYCIN. J Biol Chem. 1964 Nov;239:3826–3833. [PubMed] [Google Scholar]
  16. Yarmolinsky M. B., Haba G. L. INHIBITION BY PUROMYCIN OF AMINO ACID INCORPORATION INTO PROTEIN. Proc Natl Acad Sci U S A. 1959 Dec;45(12):1721–1729. doi: 10.1073/pnas.45.12.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]

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