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Molecular and Cellular Biology, April 2005, p. 3117-3126, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3117-3126.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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 Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan2

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 TCTP's modulation process is discussed.


* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, 128 Yen-Jiou Yuan Rd., Section 2, Nankang, Taipei 11529, Taiwan. Phone: 886-2-2789-9228. Fax: 886-2-2782-6085. E-mail: imbyy{at}ccvax.sinica.edu.tw.


Molecular and Cellular Biology, April 2005, p. 3117-3126, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3117-3126.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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