QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 3, 1287-1296, March 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E03-07-0512v1 15/3/1287    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, Z. Articles by Wu, M. Search for Related Content PubMed PubMed Citation Articles by Song, Z. Articles by Wu, M.

A Single Amino Acid Change (Asp 53 Ala53) Converts Survivin from Anti-apoptotic to Pro-apoptotic

Department of Molecular and Cell Biology, Key Laboratory of Structural Biology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China 230027

Submitted July 22, 2003; Revised November 29, 2003; Accepted November 30, 2003
Monitoring Editor: Suzanne Pfeffer

Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has been implicated in both apoptosis inhibition and cell cycle control. Recently, Survivin has attracted growing attention because of its tumor-specific expression and potential applications in tumor therapy. However, its inhibitory mechanism and subcellular localization remain controversial. Here, we report a novel Survivin mutant Surv-D53A, which displays a function opposite to Survivin and a distinctive subcellular distribution compared with its wild-type counterpart. Surv-D53A was shown to induce apoptosis in a p53-independent manner, indicating that tumor suppressor p53 is not involved in its apoptosis pathway. Surv-D53A was shown to markedly sensitize apoptosis induced by TRAIL, doxorubicin, and RIP3. We also demonstrated that similar to wild-type Survivin, Surv-D53A was localized in cytoplasm in interphase and to midbody at telophase. However, it fails to colocalize in chromosomes with Aurora-B in metaphase as wt-Survivin. Surv-D53A mutant is less stable than wt-Survivin and is degraded more rapidly by ubiquitin-proteasome pathway. Additionally, we found that Surv-D53A interacts with wt-Survivin to form heterodimer or with itself to form mutant homodimer, which may account for the loss of its antiapoptotic function. Finally, unlike Survivin^*Survivin, neither Surv-D53A^*Survivin nor Surv-D53A^*Surv-D53A is able to bind to Smac/DIABLO, which may explain the underlying mechanism for its abolishment of antiapoptotic activity of Survivin.

^* Corresponding author. E-mail address: wumian88{at}yahoo.com.

This article has been cited by other articles:

				Z. Yue, A. Carvalho, Z. Xu, X. Yuan, S. Cardinale, S. Ribeiro, F. Lai, H. Ogawa, E. Gudmundsdottir, R. Gassmann, et al. Deconstructing Survivin: comprehensive genetic analysis of Survivin function by conditional knockout in a vertebrate cell line J. Cell Biol., October 20, 2008; 183(2): 279 - 296. [Abstract] [Full Text] [PDF]

				J. Wang, L. Yang, J. Yang, K. Kuropatwinski, W. Wang, X.-Q. Liu, J. Hauser, and M. G. Brattain Transforming Growth Factor {beta} Induces Apoptosis through Repressing the Phosphoinositide 3-Kinase/AKT/Survivin Pathway in Colon Cancer Cells Cancer Res., May 1, 2008; 68(9): 3152 - 3160. [Abstract] [Full Text] [PDF]

				J. Choi, Y. K. Hwang, K. W. Sung, S. H. Lee, K. H. Yoo, H. L. Jung, H. H. Koo, H.-J. Kim, H. J. Kang, H. Y. Shin, et al. Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia Blood, January 15, 2007; 109(2): 471 - 477. [Abstract] [Full Text] [PDF]