Mcl-1和TCTP交互作用之功能探討
Functional Characterization of Mcl-1 and TCTP Interaction
Date Issued
2005
Date
2005
Author(s)
Liu, Hsuan
DOI
en-US
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 regulate Mcl-1 synthesis. While 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 over-expression of TCTP augmented the protein stability of Mcl-1, knockdown expression of TCTP by RNA interference destabilized Mcl-1. Consistently, targeted ablation of the TCTP gene led to a reduced level of 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 anti-apoptotic activity. Taken together, these results suggest that TCTP modulates Mcl-1’s anti-apoptotic activity by modulating its protein stability. The possible mechanism(s) involved in TCTP’s modulation process is discussed.
Additionally, our results demonstrated an involvement of growth signaling in modulating the expression and subcellular localization of Mcl-1 and TCTP. Both proteins, which generally locate in the cytosol of rapidly growing cells, could be detected in the nuclear compartment when cells were deprived of serum. Furthermore, interaction with TCTP may be an important determinant in regulating the localization of Mcl-1. However, the functional significance of the nuclear localization of these proteins is not fully understood and awaits further investigation.
Subjects
訊號傳遞
細胞凋亡
signal transduction
apoptosis
Type
other
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