| Texto completo | |
| Autor(es): |
Alves, Juliano
[1]
;
Wurdak, Heiko
[2]
;
Garay-Malpartida, Humberto M.
[3]
;
Harris, Jennifer L.
[4, 1]
;
Occhiucci, Joao M.
[3]
;
Belizario, Jose E.
[3]
;
Li, Jun
[4]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 - USA
[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 - USA
[3] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil
[4] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 - USA
Número total de Afiliações: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Biochemical and Biophysical Research Communications; v. 384, n. 4, p. 495-500, JUL 10 2009. |
| Citações Web of Science: | 1 |
| Resumo | |
Caspases are central players in proteolytic pathways that regulate cellular processes Such as apoptosis and differentiation. To accelerate the discovery of novel caspase substrates we developed a method combining in silico screening and in vitro validation. With this approach, we identified TAH15 as a novel caspase Substrate in a trial Study. We find that TAF15 was specifically cleaved by caspases-3 and -7. Site-directed mutagenesis revealed the consensus sequence (106)DQPD/Y(110) as the only site recognized by these caspases. Surprisingly, TAF15 was cleaved at more than one site in staurosporine-treated Jurkat cells. In addition, we generated two oncogenic TAF15-CIZ/NMP4-fused proteins which have been found in acute myeloid leukemia and demonstrate that caspases-3 and -7 cleave the fusion proteins at one single site. Broad application of this combination approach should expedite identification of novel caspase-interacting proteins and provide new insights into the regulation of caspase pathways leading to cell death in normal and cancer cells. (C) 2009 Elsevier Inc. All rights reserved. (AU) | |
| Processo FAPESP: | 01/01000-7 - Análise da expressão de genes e proteínas e da atividade de enzimas caspases em células do músculo esquelético durante a caquexia induzida por tumores malignos e citocinas |
| Beneficiário: | José Ernesto Belizario |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |