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Publication : Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP.

First Author  Liu H Year  2005
Journal  Mol Cell Biol Volume  25
Issue  8 Pages  3117-26
PubMed ID  15798198 Mgi Jnum  J:97637
Mgi Id  MGI:3575967 Doi  10.1128/MCB.25.8.3117-3126.2005
Citation  Liu H, et al. (2005) Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP. Mol Cell Biol 25(8):3117-26
abstractText  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.
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