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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 Gartel, Andrei L.

PloS one, 2013-01, Vol.8 (1), p.e53263-e53263 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib
Autor: Gelman, Julia S ; Sironi, Juan ; Berezniuk, Iryna ; Dasgupta, Sayani ; Castro, Leandro M ; Gozzo, Fabio C ; Ferro, Emer S ; Fricker, Lloyd D
Gartel, Andrei L.
Assuntos: Amino Acid Sequence ; Amino acids ; Antineoplastic Agents - pharmacology ; Apoptosis ; Autophagy ; Biological effects ; Biology ; Boronic Acids - pharmacology ; Bortezomib ; Cancer ; Cell death ; Cell Line, Tumor ; HEK293 Cells ; Humans ; Hydrophobicity ; Inhibitors ; Intracellular ; Kidney transplantation ; Medicine ; Molecular Sequence Data ; Multiple myeloma ; Neuroblastoma - drug therapy ; Neuroblastoma - pathology ; Neurosciences ; Peptides ; Peptides - analysis ; Peptides - metabolism ; Phagocytosis ; Pharmacology ; Physiology ; Proteasome Inhibitors - pharmacology ; Proteasomes ; Proteins ; Proteomics ; Pyrazines - pharmacology ; Signal transduction ; Studies
É parte de: PloS one, 2013-01, Vol.8 (1), p.e53263-e53263
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
Conceived and designed the experiments: JSG JS IB SD LDF. Performed the experiments: JSG JS IB SD LMC. Analyzed the data: JSG JS IB SD LDF. Contributed reagents/materials/analysis tools: FCG ESF. Wrote the paper: JSG ESF LDF.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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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 Gartel, Andrei L.

United States: Public Library of Science

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