Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
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]
Total Authors: 7
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: Biochemical and Biophysical Research Communications; v. 384, n. 4, p. 495-500, JUL 10 2009.
Web of Science Citations: 1
Abstract

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)