The novel tumor suppressor p33ING2 enhances UVB-induced apoptosis in human melanoma cells.
The roles of p33ING2 as a tumor suppressor candidate have been shown through regulation of gene transcription, induction of cell cycle arrest, and apoptosis. As p33ING2 shares 58.9% homology with p33ING1b, we hypothesized that p33ING2 shares functional similarities with p33ING1b. We previously found that p33ING1b cooperates with p53 to enhance UVB-induced apoptosis. Here, we report that overexpression of p33ING2 enhanced apoptosis in UVB-irradiated and non-irradiated melanoma MMRU cells. We demonstrate that enhancement of apoptosis by p33ING2 requires the presence of functional p53. Furthermore, we found that overexpression of p33ING2 significantly downregulated the expression of Bcl-2 after UVB irradiation, resulting in an increased Bax/Bcl-2 ratio. Moreover, we found that p33ING2 promoted Bax translocation to mitochondria, altered the mitochondrial membrane potential, and induced cytochrome c release and thus the activation of caspases 9 and 3. In addition, we showed that under non-stress conditions p33ING2 upregulates Fas expression and activates caspase 8. Taken together, we demonstrate that p33ING2 cooperates with p53 to regulate apoptosis via activation of both the mitochondrial/intrinsic and death-receptor/extrinsic apoptotic pathways.
Chin
Mei Yieng
MY
Department of Medicine, Division of Dermatology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Ng
Kin Cheung P
KC
Li
Gang
G
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology* / Q000528:radiation effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000502:physiology* / Q000528:radiation effects; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; D018398:Homeodomain Proteins; C444654:ING2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D045304:Cytochromes c; D020169:Caspases