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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.
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页码:940 / 945
页数:6
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