Alterations of the Intracellular Peptidome in Response to the Proteasome Inhibitor Bortezomib

Julia S. Gelman, Juan Sironi, Iryna Berezniuk, Sayani Dasgupta, Leandro M. Castro, Fabio C. Gozzo, Emer S. Ferro, Lloyd D. Fricker

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Bortezomib is an antitumor drug that competitively inhibits proteasome beta-1 and beta-5 subunits. While the impact of bortezomib on protein stability is known, the effect of this drug on intracellular peptides has not been previously explored. A quantitative peptidomics technique was used to examine the effect of treating human embryonic kidney 293T (HEK293T) cells with 5-500 nM bortezomib for various lengths of time (30 minutes to 16 hours), and human neuroblastoma SH-SY5Y cells with 500 nM bortezomib for 1 hour. Although bortezomib treatment decreased the levels of some intracellular peptides, the majority of peptides were increased by 50-500 nM bortezomib. Peptides requiring cleavage at acidic and hydrophobic sites, which involve beta-1 and -5 proteasome subunits, were among those elevated by bortezomib. In contrast, the proteasome inhibitor epoxomicin caused a decrease in the levels of many of these peptides. Although bortezomib can induce autophagy under certain conditions, the rapid bortezomib-mediated increase in peptide levels did not correlate with the induction of autophagy. Taken together, the present data indicate that bortezomib alters the balance of intracellular peptides, which may contribute to the biological effects of this drug.

Original languageEnglish (US)
Article numbere53263
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 15 2013

Fingerprint

Proteasome Inhibitors
proteasome endopeptidase complex
peptides
Peptides
autophagy
drugs
Autophagy
Proteasome Endopeptidase Complex
kidney cells
Bortezomib
quantitative analysis
Protein Stability
HEK293 Cells
Neuroblastoma
Pharmaceutical Preparations
Antineoplastic Agents
Kidney

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gelman, J. S., Sironi, J., Berezniuk, I., Dasgupta, S., Castro, L. M., Gozzo, F. C., ... Fricker, L. D. (2013). Alterations of the Intracellular Peptidome in Response to the Proteasome Inhibitor Bortezomib. PLoS One, 8(1), [e53263]. https://doi.org/10.1371/journal.pone.0053263

Alterations of the Intracellular Peptidome in Response to the Proteasome Inhibitor Bortezomib. / Gelman, Julia S.; Sironi, Juan; Berezniuk, Iryna; Dasgupta, Sayani; Castro, Leandro M.; Gozzo, Fabio C.; Ferro, Emer S.; Fricker, Lloyd D.

In: PLoS One, Vol. 8, No. 1, e53263, 15.01.2013.

Research output: Contribution to journalArticle

Gelman, JS, Sironi, J, Berezniuk, I, Dasgupta, S, Castro, LM, Gozzo, FC, Ferro, ES & Fricker, LD 2013, 'Alterations of the Intracellular Peptidome in Response to the Proteasome Inhibitor Bortezomib', PLoS One, vol. 8, no. 1, e53263. https://doi.org/10.1371/journal.pone.0053263
Gelman JS, Sironi J, Berezniuk I, Dasgupta S, Castro LM, Gozzo FC et al. Alterations of the Intracellular Peptidome in Response to the Proteasome Inhibitor Bortezomib. PLoS One. 2013 Jan 15;8(1). e53263. https://doi.org/10.1371/journal.pone.0053263
Gelman, Julia S. ; Sironi, Juan ; Berezniuk, Iryna ; Dasgupta, Sayani ; Castro, Leandro M. ; Gozzo, Fabio C. ; Ferro, Emer S. ; Fricker, Lloyd D. / Alterations of the Intracellular Peptidome in Response to the Proteasome Inhibitor Bortezomib. In: PLoS One. 2013 ; Vol. 8, No. 1.
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