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FKBP38 protects Bcl-2 from caspase-dependent degradation

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FKBP38 protects Bcl-2 from caspase-dependent degradation

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dc.contributor.author Choi, Bo-Hwa
dc.contributor.author Feng, Lin
dc.contributor.author Yoon, Ho Sup
dc.date.accessioned 2012-10-29T08:06:41Z
dc.date.available 2012-10-29T08:06:41Z
dc.date.copyright 2010
dc.date.issued 2012-10-29
dc.identifier.citation Choi, B. H., Feng, L., & Yoon, H. S. (2010). FKBP38 protects Bcl-2 from caspase-dependent degradation. Journal of Biological Chemistry, 285(13), 9770-9779.
dc.identifier.uri http://hdl.handle.net/10220/8819
dc.description.abstract The cellular processes that regulate Bcl-2 at the posttranslational levels are as important as those that regulate bcl-2 synthesis. Previously we demonstrated that the suppression of FK506-binding protein 38 (FKBP38) contributes to the instability of Bcl-2 or leaves Bcl-2 unprotected from degradation in an unknown mechanism. Here, we studied the underlying molecular mechanism mediating this process. We first showed that Bcl-2 binding-defective mutants of FKBP38 fail to accumulate Bcl-2 protein. We demonstrated that the FKBP38-mediated Bcl-2 stability is specific as the levels of other anti-apoptotic proteins such as Bcl-XL and Mcl-1 remained unaffected. FKBP38 enhanced the Bcl-2 stability under the blockade of de novo protein synthesis, indicating it is posttranslational. We showed that the overexpression of FKBP38 attenuates reduction rate of Bcl-2, thus resulting in an increment of the intracellular Bcl-2 level, contributing to the resistance of apoptotic cell death induced by the treatment of kinetin riboside, an anticancer drug. Caspase inhibitors markedly induced the accumulation of Bcl-2. In caspase-3-activated cells, the knockdown of endogenous FKBP38 by small interfering RNA resulted in Bcl-2 down-regulation as well, which was significantly recovered by the treatment with caspase inhibitors or overexpression of FKBP38. Finally we presented that the Bcl-2 cleavage by caspase-3 is blocked when Bcl-2 binds to FKBP38 through the flexible loop. Taken together, these results suggest that FKBP38 is a key player in regulating the function of Bcl-2 by antagonizing caspase-dependent degradation through the direct interaction with the flexible loop domain of Bcl-2, which contains the caspase cleavage site.
dc.language.iso en
dc.relation.ispartofseries Journal of biological chemistry
dc.rights © 2010 The American Society for Biochemistry and Molecular Biology, Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Biological Chemistry, The American Society for Biochemistry and Molecular Biology, 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/10.1074/jbc.M109.032466].
dc.subject DRNTU::Science::Biological sciences.
dc.title FKBP38 protects Bcl-2 from caspase-dependent degradation
dc.type Journal Article
dc.contributor.school School of Biological Sciences
dc.identifier.doi http://dx.doi.org/10.1074/jbc.M109.032466
dc.description.version Accepted version

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