| Texto completo | |
| Autor(es): |
Berti, Denise A.
[1]
;
Morano, Cain
[2]
;
Russo, Lilian C.
[3]
;
Castro, Leandro M.
[1]
;
Cunha, Fernanda M.
[4, 1]
;
Zhang, Xin
[2]
;
Sironi, Juan
[2]
;
Klitzke, Clecio F.
[5]
;
Ferro, Emer S.
[1]
;
Fricker, Lloyd D.
[2]
Número total de Autores: 10
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Dept Dev & Cell Biol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil
[2] Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 - USA
[3] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Dept Biochem, BR-04044020 Sao Paulo - Brazil
[5] Butantan Inst, CAT CEPID, Ctr Appl Toxicol, BR-05503900 Sao Paulo - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Biological Chemistry; v. 284, n. 21, p. 14105-14116, May 2009. |
| Área do conhecimento: | Ciências Biológicas - Morfologia |
| Citações Web of Science: | 42 |
| Assunto(s): | Sistema urogenital Rim Oligopeptídeos Metaloproteases Metaloendopeptidases |
| Resumo | |
Thimet oligopeptidase (EC 3.4.24.15; EP24.15) is an intracellular enzyme that has been proposed to metabolize peptides within cells, thereby affecting antigen presentation and G protein- coupled receptor signal transduction. However, only a small number of intracellular substrates of EP24.15 have been reported previously. Here we have identified over 100 peptides in human embryonic kidney 293 (HEK293) cells that are derived from intracellular proteins; many but not all of these peptides are substrates or products of EP24.15. First, cellular peptides were extracted from HEK293 cells and incubated in vitro with purified EP24.15. Then the peptides were labeled with isotopic tags and analyzed by mass spectrometry to obtain quantitative data on the extent of cleavage. A related series of experiments tested the effect of overexpression of EP24.15 on the cellular levels of peptides in HEK293 cells. Finally, synthetic peptides that corresponded to 10 of the cellular peptides were incubated with purified EP24.15 in vitro, and the cleavage was monitored by high pressure liquid chromatography and mass spectrometry. Many of the EP24.15 substrates identified by these approaches are 9-11 amino acids in length, supporting the proposal that EP24.15 can function in the degradation of peptides that could be used for antigen presentation. However, EP24.15 also converts some peptides into products that are 8-10 amino acids, thus contributing to the formation of peptides for antigen presentation. In addition, the intracellular peptides described here are potential candidates to regulate protein interactions within cells. (AU) | |
| Processo FAPESP: | 04/04933-2 - Biologia celular molecular de oligopeptidases |
| Beneficiário: | Emer Suavinho Ferro |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |