Stabilization and enhancement of the antiapoptotic activity of Mcl-1 by TCTP
Journal
Molecular and Cellular Biology
Journal Volume
25
Journal Issue
8
Pages
3117-3126
Date Issued
2005
Author(s)
Abstract
Mcl-1 is one Bcl-2 family member that plays a pivotal role in animal development. The extremely labile nature of the Mcl-1 protein itself and the fact that the Mcl-1 level is a critical determinant in various cell survival pathways suggest that cellular processes that regulate Mcl-1 stability are as important as those that regulate Mcl-1 synthesis. Although transcriptional stimulation of Mcl-1 synthesis in response to various stimuli has been well documented, regulation of Mcl-1 stability has been hardly explored. In this study, we identified that the translationally controlled tumor protein (TCTP) was one cellular factor that interacted with Mcl-1 and modulated Mcl-1 stability. While overexpression of TCTP augmented the protein stability of Mcl-1, knockdown expression of TCTP by RNA interference destabilized Mcl-1. Furthermore, TCTP stabilized Mcl-1 through interfering with Mcl-1's degradation by the ubiquitin-dependent proteasome degradation pathway, and the TCTP binding-defective mutant of Mcl-1 (K257V) was much more susceptible to degradation and manifested a compromised antiapoptotic activity. Taken together, these results suggest that TCTP modulates Mcl-1's antiapoptotic activity by modulating its protein stability. The possible mechanism(s) involved in TCTP's modulation process is discussed. Copyright ? 2005, American Society for Microbiology. All Rights Reserved.
Other Subjects
proteasome; protein mcl 1; tumor protein; ubiquitin; animal cell; apoptosis; article; controlled study; gene mutation; gene overexpression; molecular stability; mouse; nonhuman; priority journal; protein degradation; protein interaction; protein stability; RNA interference; translation initiation; translation regulation; Amino Acid Sequence; Amino Acid Substitution; Animals; Apoptosis; Binding Sites; Cell Line; Down-Regulation; Lysine; Mice; Molecular Sequence Data; Mutation; Neoplasm Proteins; Proteasome Endopeptidase Complex; Protein Interaction Mapping; Proto-Oncogene Proteins c-bcl-2; RNA Interference; RNA, Small Interfering; Trans-Activation (Genetics); Tumor Markers, Biological; Two-Hybrid System Techniques; Ubiquitin; Animalia
Type
journal article
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