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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effect of Protein Denaturation and Enzyme Inhibitors on Proteasomal-Mediated Production of Peptides in Human Embryonic Kidney Cells

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Author(s):
Dasgupta, Sayani [1] ; Fishman, Michael A. [1] ; Castro, Leandro M. [2] ; Tashima, Alexandre K. [3] ; Ferro, Emer S. [4] ; Fricker, Lloyd D. [5, 1]
Total Authors: 6
Affiliation:
[1] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 - USA
[2] Sao Paulo State Univ, Biosci Inst, Coastal Campus, BR-11330900 Sao Vicente, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, BR-04023901 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Biomed Sci Inst, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil
[5] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 - USA
Total Affiliations: 5
Document type: Journal article
Source: BIOMOLECULES; v. 9, n. 6 JUN 2019.
Web of Science Citations: 1
Abstract

Peptides produced by the proteasome have been proposed to function as signaling molecules that regulate a number of biological processes. In the current study, we used quantitative peptidomics to test whether conditions that affect protein stability, synthesis, or turnover cause changes in the levels of peptides in Human Embryonic Kidney 293T (HEK293T) cells. Mild heat shock (42 degrees C for 1 h) or treatment with the deubiquitinase inhibitor b-AP15 led to higher levels of ubiquitinated proteins but did not significantly increase the levels of intracellular peptides. Treatment with cycloheximide, an inhibitor of protein translation, did not substantially alter the levels of intracellular peptides identified herein. Cells treated with a combination of epoxomicin and bortezomib showed large increases in the levels of most peptides, relative to the levels in cells treated with either compound alone. Taken together with previous studies, these results support a mechanism in which the proteasome cleaves proteins into peptides that are readily detected in our assays (i.e., 6-37 amino acids) and then further degrades many of these peptides into smaller fragments. (AU)

FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
Grantee:Emer Suavinho Ferro
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/20106-9 - Peptidomics of Brazilian snake and spider venoms
Grantee:Alexandre Keiji Tashima
Support Opportunities: Regular Research Grants