![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on March 1, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 22, 2003
Revised on November 29, 2003
Accepted on November 30, 2003
Ala53) Converts Survivin from anti-apoptotic to pro-apoptotic
1 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
2 Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China 230027
* Corresponding author. E-mail address: wumian88{at}yahoo.com.
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 due to 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.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
