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

0481658 - FGÚ 2018 RIV US eng J - Journal Article
Kalábová, Dana - Šmídová, Aneta - Petrvalská, Olivia - Alblová, Miroslava - Košek, Dalibor - Man, Petr - Obšil, Tomáš - Obšilová, Veronika
Human procaspase-2 phosphorylation at both S139 and S164 is required for 14-3-3 binding.
Biochemical and Biophysical Research Communications. Roč. 493, č. 2 (2017), s. 940-945. ISSN 0006-291X. E-ISSN 1090-2104
R&D Projects: GA ČR(CZ) GA17-00726S; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:67985823 ; RVO:61388971
Keywords : procaspase-2 * 14-3-3 * protein-protein interaction * phosphorylation * caspase-2
OECD category: Biochemistry and molecular biology; Biochemistry and molecular biology (MBU-M)
Impact factor: 2.559, year: 2017

Procaspase-2 phosphorylation at several residues prevents its activation and blocks apoptosis. This process involves procaspase-2 phosphorylation at S164 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 S139 and S164. 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.
Permanent Link: http://hdl.handle.net/11104/0277183