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

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 TAF15 as...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-07, Vol.384 (4), p.495-500
Main Authors: Alves, Juliano, Wurdak, Heiko, Garay-Malpartida, Humberto M., Harris, Jennifer L., Occhiucci, João M., Belizário, José E., Li, Jun
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Acute myeloid leukemia
APOPTOSIS
Caspase 3 - metabolism
Caspase substrate
GENE REGULATION
Humans
IN VITRO
Jurkat Cells
Leukemia, Myeloid, Acute - metabolism
MUTAGENESIS
MYELOID LEUKEMIA
Oncogene Proteins, Fusion - genetics
Oncogene Proteins, Fusion - metabolism
PROTEINS
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Substrate Specificity
SUBSTRATES
TAF15
TAF15–CIZ/NMP4
TATA-Binding Protein Associated Factors - genetics
TATA-Binding Protein Associated Factors - metabolism
Trans-Activators - genetics
Trans-Activators - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 TAF15 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 106DQPD/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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.05.009