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FK506, an Immunosup...
FK506, an Immunosuppressive Drug, Induces Autophagy by Binding to the V-ATPase Catalytic Subunit A in Neuronal Cells
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- Kim, Dongyoung (author)
- Yonsei University
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- Hwang, Hui Yun (author)
- Yonsei University
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- Kim, Young Jin (author)
- Korea Basic Science Institute
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Lee, Ju Yeon (author)
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- Yoo, Jong Shin (author)
- Korea Basic Science Institute
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- Marko-Varga, György (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Kwon, Ho Jeong (author)
- Yonsei University
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(creator_code:org_t)
- 2016-11-17
- 2017
- English 10 s.
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 16:1, s. 55-64
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http://dx.doi.org/10...
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Abstract
Subject headings
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- The drug FK506 (tacrolimus, fujimycin) exerts its immunosuppressive effects by regulating the nuclear factor of the activated T-cell (NFAT) family of transcription factors. However, FK506 also exhibits neuroprotective effects, but its direct target proteins that mediate these effects have not been determined. To identify the target proteins responsible for FK506's neuroprotective effects, the drug affinity responsive target stability (DARTS) method was performed using label-free FK506, and LC-MS/MS analysis of the FK506-treated proteome was also performed. Using DARTS and LC-MS/MS analyses in combination with reference studies, V-ATPase catalytic subunit A (ATP6V1A) was identified as a new target protein of FK506. The biological relevance of ATP6V1A in mediating the neuroprotective effects of FK506 was validated by analyzing FK506 activity with respect to autophagy via acridine orange staining and transcription factor EB (TFEB) translocation assay. These analyses demonstrated that the binding of FK506 with ATP6V1A induces autophagy by activating the translocation of TFEB from the cytosol into the nucleus. Because autophagy has been identified as a mechanism for treating neurodegenerative diseases and because we have demonstrated that FK506 induces autophagy, this study demonstrates that FK506 is a possible new therapy for treating neurodegenerative diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- autophagy
- DARTS
- FK506
- LC-MS/MS
- neuroprotective activity
- TFEB translocation
- V-ATPase
Publication and Content Type
- art (subject category)
- ref (subject category)
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