An alternative splice form of CMTM8 induces apoptosis.
Previous studies have demonstrated that the chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 8 (CMTM8) protein accelerates the ligand-induced clearance of epidermal growth factor receptor (EGFR) from the cell surface. The absence of EGFR-mediated signaling induces cells to undergo apoptosis via caspase-dependent and -independent pathways. Here we report the cloning and sequencing of an alternative splice form of CMTM8, obtained from a human blood cDNA library, that utilizes apoptotic pathways distinct from CMTM8. The alternative splice variant arises from a deletion of exon 2 that prevents the expression of a full-length MARVEL domain, and cytosolic YXXPhi motifs. Nevertheless, CMTM8-v2 maintains the ability to induce apoptosis via caspase-dependent and -independent pathways to inhibit cell growth and colony formation. CMTM8 and CMTM8-v2 display different expression profiles and distinct subcellular localization patterns, while operating via different mechanisms to induce apoptosis. CMTM8-v2 did not affect EGFR internalization, implying that the MARVEL domain and/or the cytosolic YXXPhi motifs are necessary for CMTM8 to accelerate ligand-induced EGFR internalization.
Li
Dan
D
Lab of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, 38# Xueyuan Road, Beijing 100083, PR China.
Jin
Caining
C
Yin
Caihua
C
Zhang
Yingmei
Y
Pang
Bo
B
Tian
Linjie
L
Han
Wenling
W
Ma
Dalong
D
Wang
Ying
Y
D017398:Alternative Splicing / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D018925:Chemokines / Q000737:chemistry / Q000235:genetics*; D003580:Cytochromes / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004705:Endocytosis; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D053078:Membrane Potential, Mitochondrial; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051033:Apoptosis Inducing Factor; C507076:CMTM8 protein, human; D018925:Chemokines; D003580:Cytochromes; D018076:DNA, Complementary; D062792:MARVEL Domain-Containing Proteins; D051028:bcl-2-Associated X Protein; D066246:ErbB Receptors; D020169:Caspases