The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis.
Amyloid precursor protein (APP)-derived intracellular domain (AICD) has a cytotoxic effect on neuronal cells and also participates in the regulation of gene transactivation. However, the precise molecular mechanisms behind the AICD-mediated apoptosis remain unknown. In this study, we have demonstrated that AICD interacts with p53 and enhances its transcriptional and pro-apoptotic functions. p53 was induced to be accumulated and associated with APP in response to cisplatin. Indeed, APP-C57 was co-immunoprecipitated with the endogenous p53. Enforced expression of APP-C57 or APP-C59 in U2OS cells bearing wild-type p53 led to an increase in number of apoptotic cells, whereas they had undetectable effects on p53-deficient H1299 cells, suggesting that AICD contributes to the activation of the p53-mediated apoptotic pathway. Consistent with this notion, the p53-mediated transcriptional activation and apoptosis were significantly enhanced by co-expression with APP-C57 or APP-C59. Thus, our present results strongly suggest that AICD triggers apoptosis through the p53-dependent mechanisms.
Ozaki
Toshinori
T
Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
Li
Yuanyuan
Y
Kikuchi
Hironobu
H
Tomita
Taisuke
T
Iwatsubo
Takeshi
T
Nakagawara
Akira
A
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53