TY - JOUR
T1 - Cell surface beta 1, 4-galactosyltransferase 1 promotes apoptosis by inhibiting epidermal growth factor receptor pathway
AU - Li, Zejuan
AU - Zong, Hongliang
AU - Kong, Xiangfei
AU - Zhang, Si
AU - Wang, Hanzhou
AU - Sun, Qing
AU - Gu, Jianxin
PY - 2006/10
Y1 - 2006/10
N2 - Our previous studies have shown that overexpression of β1,4-galactosyltransferase1 (β1,4GT1) leads to increased apoptosis induced by cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells. However, the role of β1,4GT1 in apoptosis remains unclear. Here we demonstrated that cell surface β1,4GT1 inhibited the autophosphorylation of epidermal growth factor receptor (EGFR) especially at Try 1068. The phosphorylation of protein kinase B (PKB/Akt) and extracellular signal-regulated protein kinase1/2 (ERK1/2), which are downstream molecules of EGFR, were also reduced in cell surface β1,4GT1-overexpressing cells. Furthermore, the translocations of Bad and Bax that are regulated by PKB/Akt and ERK1/2 were also increased in these cells. As a result, the release of cytochrome c from mitochondria to cytosol was increased and caspase-3 was activated. In contrast, RNAi-mediated knockdown of β1,4GT1 increased the autophosphorylation of EGFR. These results demonstrated that cell surface β1,4GT1 may negatively regulate cell survival possibly through inhibiting and modulating EGFR signaling pathway.
AB - Our previous studies have shown that overexpression of β1,4-galactosyltransferase1 (β1,4GT1) leads to increased apoptosis induced by cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells. However, the role of β1,4GT1 in apoptosis remains unclear. Here we demonstrated that cell surface β1,4GT1 inhibited the autophosphorylation of epidermal growth factor receptor (EGFR) especially at Try 1068. The phosphorylation of protein kinase B (PKB/Akt) and extracellular signal-regulated protein kinase1/2 (ERK1/2), which are downstream molecules of EGFR, were also reduced in cell surface β1,4GT1-overexpressing cells. Furthermore, the translocations of Bad and Bax that are regulated by PKB/Akt and ERK1/2 were also increased in these cells. As a result, the release of cytochrome c from mitochondria to cytosol was increased and caspase-3 was activated. In contrast, RNAi-mediated knockdown of β1,4GT1 increased the autophosphorylation of EGFR. These results demonstrated that cell surface β1,4GT1 may negatively regulate cell survival possibly through inhibiting and modulating EGFR signaling pathway.
KW - Apoptosis
KW - CycloheximideCHX
KW - Epidermal growth factor receptor EGFR
KW - β1,4-galactosyltransferase1(β1,4GT1)
UR - http://www.scopus.com/inward/record.url?scp=33750918116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750918116&partnerID=8YFLogxK
U2 - 10.1007/s11010-006-9198-3
DO - 10.1007/s11010-006-9198-3
M3 - Article
C2 - 16786197
AN - SCOPUS:33750918116
SN - 0300-8177
VL - 291
SP - 69
EP - 76
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -