TAF15 and the leukemia-associated fusion protein TAF15-CIZ/NMP4 are cleaved by caspases-3 and-7

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]

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

• 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