CMTM8 induces caspase-dependent and -independent apoptosis through a mitochondria-mediated pathway

✍ Scribed by Caining Jin; Ying Wang; Wenling Han; Yingmei Zhang; Qihua He; Dan Li; Caihua Yin; Linjie Tian; Dazhen Liu; Quanshen Song; Dalong Ma

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 515 KB
• Volume: 211
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20914

✦ Synopsis

Abstract

The mitochondria‐mediated apoptotic pathway is regulated by members of the Bcl‐2 family. Epidermal growth factor (EGF) induces Bad phosphorylation at Ser~112~ 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‐S~112~ 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 ERK1/2phosphorylation 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. J. Cell. Physiol. 211: 112–120, 2007. © 2006 Wiley‐Liss, Inc.