CMTM8 induces caspase-dependent and -independent apoptosis through a mitochondria-mediated pathway.
The mitochondria-mediated apoptotic pathway is regulated by members of the Bcl-2 family. Epidermal growth factor (EGF) induces Bad phosphorylation at Ser112 via mitogen-activated protein kinase (MAPK), impairing its binding to Bcl-2 and Bcl-xL and interfering with their anti-apoptotic functions. In the current study, we utilized Western blot, immunofluorescence, flow cytometry, and confocal microscopy to examine the effects of CMTM8 overexpression on apoptosis. Our data indicated levels of Bad-S112 phosphorylation were lower in CMTM8-transfected cells compared to pCDB-transfected cells. Caspase-dependent and independent mediated apoptosis, induced by CMTM8 overexpression, was facilitated by the mitochondria and inhibited by knockdown of Bad or overexpression of Bcl-xL. Previous research in our laboratory also demonstrated CMTM8 attenuated EGFR-mediated signaling pathways by decreasing ERK1/2 phosphorylation levels. These data implicate CMTM8 as a negative regulator of EGF-induced signaling, with potential use as a novel therapeutic gene for EGFR-targeted anticancer gene therapy.
Jin
Caining
C
Center for Human Disease Genomics, Peking University, Beijing, PR China.
Wang
Ying
Y
Han
Wenling
W
Zhang
Yingmei
Y
He
Qihua
Q
Li
Dan
D
Yin
Caihua
C
Tian
Linjie
L
Liu
Dazhen
D
Song
Quanshen
Q
Ma
Dalong
D
D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010957:Plasmids; D014162:Transfection; D051025:bcl-Associated Death Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D051033:Apoptosis Inducing Factor; C507076:CMTM8 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D010768:Phosphoserine; D045304:Cytochromes c; D020169:Caspases