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, National Taiwan University Medical School,1 and

Institute of Molecular Biology, Academia Sinica,2 Taipei, Taiwan

 

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-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

 

MOLECULAR AND CELLULAR BIOLOGY, Apr. 2005, p. 3117–3126

 


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