TY - JOUR
T1 - Oxidized S100A4 inhibits the activation of protein phosphatase 5 through S100A1 in MKN-45 gastric carcinoma cells
AU - Tsuchiya, Mitsumasa
AU - Yamaguchi, Fuminori
AU - Shimamoto, Seiko
AU - Fujimoto, Tomohito
AU - Tokumitsu, Hiroshi
AU - Tokuda, Masaaki
AU - Kobayashi, Ryoji
PY - 2014/12/1
Y1 - 2014/12/1
N2 - S100 proteins bind to numerous target proteins, as well as other S100 proteins and activate signaling cascades. S100 proteins can be modified by various post-translational modifications, such as phosphorylation, methylation and acety-lation. In addition, oxidation is important for modulating their activities. Previous studies have shown that S100A1 interacts with S100A4 in vit ro and in vivo. Due to this potential cross-talk among the S100 proteins, the aim of the present study was to examine whether S100A4 modulates the activity of S100A1. S100A4 was readily oxidized and formed disulfide-linked dimers and oligomers. Although non-oxidized S100A4 bound to protein phosphatase 5 (PP5), the Cu-oxidized S100A4 failed to bind PP5. Instead, the Cu-oxidized S100A4 directly interacted with S100A1 and prevented PP5 activation. Hydrogen peroxide induced S100A4 oxidation in MKN-45 gastric adenocarcinoma cells and decreased S100A1-PP5 interaction, resulted in the inhibition of PP5 activation by S100A1. These data indicate that oxidized S100A4 regulates PP5 activity in a unique manner under oxidative stress conditions.
AB - S100 proteins bind to numerous target proteins, as well as other S100 proteins and activate signaling cascades. S100 proteins can be modified by various post-translational modifications, such as phosphorylation, methylation and acety-lation. In addition, oxidation is important for modulating their activities. Previous studies have shown that S100A1 interacts with S100A4 in vit ro and in vivo. Due to this potential cross-talk among the S100 proteins, the aim of the present study was to examine whether S100A4 modulates the activity of S100A1. S100A4 was readily oxidized and formed disulfide-linked dimers and oligomers. Although non-oxidized S100A4 bound to protein phosphatase 5 (PP5), the Cu-oxidized S100A4 failed to bind PP5. Instead, the Cu-oxidized S100A4 directly interacted with S100A1 and prevented PP5 activation. Hydrogen peroxide induced S100A4 oxidation in MKN-45 gastric adenocarcinoma cells and decreased S100A1-PP5 interaction, resulted in the inhibition of PP5 activation by S100A1. These data indicate that oxidized S100A4 regulates PP5 activity in a unique manner under oxidative stress conditions.
KW - MKN-45
KW - Oxidative stress
KW - Protein phosphatase 5
KW - S100 protein
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UR - http://www.scopus.com/inward/citedby.url?scp=84908071059&partnerID=8YFLogxK
U2 - 10.3892/ijmm.2014.1947
DO - 10.3892/ijmm.2014.1947
M3 - Article
C2 - 25269953
AN - SCOPUS:84908071059
VL - 34
SP - 1713
EP - 1719
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
IS - 6
ER -