title: Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib.
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.
authors: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Julia S
authors: JS
authors: Gelman
authors: Juan
authors: J
authors: Sironi
authors: Iryna
authors: I
authors: Berezniuk
authors: Sayani
authors: S
authors: Dasgupta
authors: Leandro M
authors: LM
authors: Castro
authors: Fabio C
authors: FC
authors: Gozzo
authors: Emer S
authors: ES
authors: Ferro
authors: Lloyd D
authors: LD
authors: Fricker
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000032:analysis / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D040901:Proteomics; D011719:Pyrazines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D010455:Peptides; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib