Abstract 622: Degradation of APE1 by the E3 ubiquitin ligase Parkin
| Autor: | Suganya Rangaswamy, Bithika Dhar, Timothy L. Scott, Hansruedi Büeler, Lianteng Zhi, Tadahide Izumi |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:622-622 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2013-622 |
| Popis: | The mammalian apurinic/apyrimidinic endonuclease 1 (APE1/Ref1) is a DNA repair/redox regulator protein of which cytoplasmic accumulation has been associated with tumorigenesis and poor survival outcome. APE1 is degraded through the ubiquitin/proteasome pathway and previous studies reported APE1 ubiquitination by the E3 ubiquitin ligases MDM2 and UBR3. Here we report that Parkin efficiently polyubiquitinated and degraded APE1. Parkin, a product of the PARK2 gene, is responsible for a type of early onset Parkinson's disease (PD) and has been identified as a tumor suppressor. Expression of Parkin and Pink1 enhanced APE1 ubiquitination and markedly decreased endogenous APE1 in A549, a lung adenocarcinoma cell line. APE1 degradation was blocked by incubation of the cells with MG132, a potent 26S proteasome inhibitor, and by a PD associated point mutation in the Parkin RING domain. The activity of PTEN induced-kinase 1 (Pink1) was required for APE1 degradation. Co-immunoprecipitation revealed that APE1 interacted with Parkin in the presence of Pink1. These results suggest that APE1 stability is dynamically regulated by Parkin in the cytoplasm through the N-terminal APE1 domain. Citation Format: Timothy L. Scott, Suganya Rangaswamy, Bithika Dhar, LianTeng Zhi, Hansruedi Bueler, Tadahide Izumi. Degradation of APE1 by the E3 ubiquitin ligase Parkin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 622. doi:10.1158/1538-7445.AM2013-622 |
| Databáze: | OpenAIRE |
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