Artículos de revistas
TAF15 and the leukemia-associated fusion protein TAF15-CIZ/NMP4 are cleaved by caspases-3 and-7
Fecha
2009Registro en:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.384, n.4, p.495-500, 2009
0006-291X
10.1016/j.bbrc.2009.05.009
Autor
ALVES, Juliano
WURDAK, Heiko
GARAY-MALPARTIDA, Humberto M.
HARRIS, Jennifer L.
OCCHIUCCI, Joao M.
BELIZARIO, Jose E.
LI, Jun
Institución
Resumen
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.