Stabilization and Enhancement of the Antiapoptotic Activity of Mcl-1 by TCTP Hsuan Liu,1 Hsien-Wei Peng,1 Yi-Sheng Cheng,2 Hanna S.
Yuan,2 and Hsin-Fang Yang-Yen1,2* Institute of
Molecular Medicine, Received 9 September
2004/Returned for modification 25 October 2004/Accepted 12 January 2005 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 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 MOLECULAR AND CELLULAR BIOLOGY, Apr.
2005, p. 3117–3126 |
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