Human procaspase-2 phosphorylation at both S139 and S164 is required for 14-3-3 binding

被引:14
作者
Kalabova, Dana [1 ,4 ]
Smidova, Aneta [1 ]
Petrvalska, Olivia [1 ,2 ]
Alblova, Miroslava [1 ]
Kosek, Dalibor [1 ,2 ]
Man, Petr [3 ]
Obsil, Tomas [1 ,2 ]
Obsilova, Veronika [1 ]
机构
[1] Czech Acad Sci, Div BIOCEV, Dept Struct Biol Signaling Prot, Inst Physiol, Prumyslova 595, Vestec 25250, Czech Republic
[2] Charles Univ Prague, Fac Sci, Dept Phys & Macromol Chem, Prague 12843, Czech Republic
[3] Czech Acad Sci, Inst Microbiol, BIOCEV, Prumyslova 595, Vestec 25250, Czech Republic
[4] Charles Univ Prague, Fac Med 2, V Uvalu 84, Prague 15006, Czech Republic
关键词
Procaspase-2; 14-3-3; Protein-protein interaction; PhosphoryIation; Caspase-2; NUCLEAR-LOCALIZATION; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; CASPASE-2; ACTIVATION; APOPTOSIS; PROTEIN; RECOGNITION; EXPRESSION; PRODOMAIN;
D O I
10.1016/j.bbrc.2017.09.116
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Procaspase-2 phosphorylation at several residues prevents its activation and blocks apoptosis. This process involves procaspase-2 phosphorylation at 5164 and its binding to the scaffolding protein 14-3-3. However, bioinformatics analysis has suggested that a second phosphoserine-containing motif may also be required for 14-3-3 binding. In this study, we show that human procaspase-2 interaction with 14-3-3 is governed by phosphorylation at both 5139 and 5164. Using biochemical and biophysical approaches, we show that doubly phosphorylated procaspase-2 and 14-3-3 form an equimolar complex with a dissociation constant in the nanomolar range. Furthermore, our data indicate that other regions of procaspase-2, in addition to phosphorylation motifs, may be involved in the interaction with 14-3-3. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:940 / 945
页数:6
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