Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2

The immunosuppressant FK-506 binding protein 38 (FKBP38) is localized at the mitochondrial membrane and appears to play an important role in apoptosis. Recent reports about the potential functions of FKBP38 in apoptosis appear to be controversial. To further understand the biological function of FKB...

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Main Authors: Kang, Cong Bao, Feng, Lin, Chia, Joel, Yoon, Ho Sup
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2012
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Online Access:https://hdl.handle.net/10356/94816
http://hdl.handle.net/10220/8825
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-948162023-02-28T17:03:35Z Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2 Kang, Cong Bao Feng, Lin Chia, Joel Yoon, Ho Sup School of Biological Sciences DRNTU::Science::Biological sciences The immunosuppressant FK-506 binding protein 38 (FKBP38) is localized at the mitochondrial membrane and appears to play an important role in apoptosis. Recent reports about the potential functions of FKBP38 in apoptosis appear to be controversial. To further understand the biological function of FKBP38, here, we studied its molecular characteristics and a potential regulatory role on the anti-apoptotic protein Bcl-2. Our results suggest that FKBP38 appears to show chaperone activities in the citrate synthase aggregation assays during thermal denaturation and affect solubility of Bcl-2 when they are co-expressed. The FKBP family proteins bind the immunosuppressive drug FK-506 through the FK-506 binding domain and consequently inhibit the activity of calcineurin. In this study, from our NMR studies and calcineurin assays in vitro, we demonstrate that the N-terminal fragment of FKBP38 which contains the FK-506 binding domain does not bind FK-506 at molecular level. Lastly, to investigate the effect of FKBP38 on Bcl-2, we suppressed FKBP38 by RNA interference (RNAi) of FKBP38. Our results suggest that the suppression of FKBP38 appears to make Bcl-2 unstable or unprotected from degradation in an unknown mechanism. Accepted version 2012-10-30T04:12:02Z 2019-12-06T19:02:50Z 2012-10-30T04:12:02Z 2019-12-06T19:02:50Z 2005 2005 Journal Article Kang, C. B., Feng, L., Chia, J., & Yoon, H. S. (2005). Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2. Biochemical and Biophysical Research Communications, 337(1), 30-38. 0006-291X https://hdl.handle.net/10356/94816 http://hdl.handle.net/10220/8825 10.1016/j.bbrc.2005.09.023 en Biochemical and biophysical research communications © 2005 Elsevier Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Biochemical and Biophysical Research Communications, Elsevier Inc. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bbrc.2005.09.023]. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Kang, Cong Bao
Feng, Lin
Chia, Joel
Yoon, Ho Sup
Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2
description The immunosuppressant FK-506 binding protein 38 (FKBP38) is localized at the mitochondrial membrane and appears to play an important role in apoptosis. Recent reports about the potential functions of FKBP38 in apoptosis appear to be controversial. To further understand the biological function of FKBP38, here, we studied its molecular characteristics and a potential regulatory role on the anti-apoptotic protein Bcl-2. Our results suggest that FKBP38 appears to show chaperone activities in the citrate synthase aggregation assays during thermal denaturation and affect solubility of Bcl-2 when they are co-expressed. The FKBP family proteins bind the immunosuppressive drug FK-506 through the FK-506 binding domain and consequently inhibit the activity of calcineurin. In this study, from our NMR studies and calcineurin assays in vitro, we demonstrate that the N-terminal fragment of FKBP38 which contains the FK-506 binding domain does not bind FK-506 at molecular level. Lastly, to investigate the effect of FKBP38 on Bcl-2, we suppressed FKBP38 by RNA interference (RNAi) of FKBP38. Our results suggest that the suppression of FKBP38 appears to make Bcl-2 unstable or unprotected from degradation in an unknown mechanism.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Kang, Cong Bao
Feng, Lin
Chia, Joel
Yoon, Ho Sup
format Article
author Kang, Cong Bao
Feng, Lin
Chia, Joel
Yoon, Ho Sup
author_sort Kang, Cong Bao
title Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2
title_short Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2
title_full Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2
title_fullStr Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2
title_full_unstemmed Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2
title_sort molecular characterization of fk-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein bcl-2
publishDate 2012
url https://hdl.handle.net/10356/94816
http://hdl.handle.net/10220/8825
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