ATP Binding Cassette Transporter A1 is Involved in Extracellular Secretion of Acetylated APE1/Ref-1

Autor: Yu Ran Lee, Hee Kyoung Joo, Eun Ok Lee, Hyun Sil Cho, Sunga Choi, Cuk-Seong Kim, Byeong Hwa Jeon
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 13, p 3178 (2019)
Druh dokumentu: article
ISSN: 1422-0067
35455993
DOI: 10.3390/ijms20133178
Popis: Acetylation of nuclear apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is associated with its extracellular secretion, despite the lack of an N-terminal protein secretion signal. In this study, we investigated plasma membrane targeting and translocation of APE1/Ref-1 in HEK293T cells with enhanced acetylation. While APE1/Ref-1 targeting was not affected by inhibition of the endoplasmic reticulum/Golgi-dependent secretion, its secretion was reduced by inhibitors of ATP-binding cassette (ABC) transporters, and siRNA-mediated down-regulation of ABC transporter A1. The association between APE1/Ref-1 and ABCA1 transporter was confirmed by proximal ligation assay and immunoprecipitation experiments. An APE1/Ref-1 construct with mutated acetylation sites (K6/K7R) showed reduced co-localization with ABC transporter A1. Exposure of trichostatin A (TSA) induced the acetylation of APE1/Ref-1, which translocated into membrane fraction. Taken together, acetylation of APE1/Ref-1 is considered to be necessary for its extracellular targeting via non-classical secretory pathway using the ABCA1 transporter.
Databáze: Directory of Open Access Journals
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