This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by King, F. W.
Right arrow Articles by Shtivelman, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by King, F. W.
Right arrow Articles by Shtivelman, E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2004, p. 7091-7101, Vol. 24, No. 16
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.16.7091-7101.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inhibition of Nuclear Import by the Proapoptotic Protein CC3

Frank W. King and Emma Shtivelman*

Cancer Research Institute, University of California San Francisco, San Francisco, California 94115

Received 25 January 2004/ Returned for modification 29 April 2004/ Accepted 26 May 2004

We report here that the normal cellular protein CC3/TIP30, when in excess, inhibits nuclear import in vitro and in vivo. CC3 binds directly to the karyopherins of the importin ß family in a RanGTP-insensitive manner and associates with nucleoporins in vivo. CC3 inhibits the nuclear import of proteins possessing either the classical nuclear localization signal or the M9 signal recognized by transportin. CC3 also inhibits nuclear translocation of transportin itself. Cells modified to express higher levels of CC3 have a slower rate of nuclear import and, as described earlier, show an increased sensitivity to death signals. A mutant CC3 protein lacking proapoptotic activity has a lower affinity for transportin, is displaced from it by RanGTP, and fails to inhibit nuclear import in vitro and in vivo. Together, our results support a correlation between the ability of CC3 to form a RanGTP-resistant complex with importins, inhibit nuclear import, and induce apoptosis. Significantly, a dominant-negative form of importin ß1 shown previously to inhibit multiple transport pathways induces rapid cell death, strongly indicating that inhibition of nuclear transport serves as a potent apoptotic signal.

* Corresponding author. Mailing address: Cancer Research Institute, 2340 Sutter St., San Francisco, CA 94115. Phone: (415) 502-1985. Fax: (415) 502-3179. E-mail: eshtivel{at}cc.ucsf.edu.

Molecular and Cellular Biology, August 2004, p. 7091-7101, Vol. 24, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.16.7091-7101.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhao, J., Chen, J., Lu, B., Dong, L., Wang, H., Bi, C., Wu, G., Guo, H., Wu, M., Guo, Y. (2008). TIP30 Induces Apoptosis under Oxidative Stress through Stabilization of p53 Messenger RNA in Human Hepatocellular Carcinoma. Cancer Res. 68: 4133-4141 [Abstract] [Full Text]  
  • Jiang, C., Pecha, J., Hoshino, I., Ankrapp, D., Xiao, H. (2007). TIP30 Mutant Derived from Hepatocellular Carcinoma Specimens Promotes Growth of HepG2 Cells through Up-Regulation of N-cadherin. Cancer Res. 67: 3574-3582 [Abstract] [Full Text]  
  • El Omari, K., Bird, L. E., Nichols, C. E., Ren, J., Stammers, D. K. (2005). Crystal Structure of CC3 (TIP30): IMPLICATIONS FOR ITS ROLE AS A TUMOR SUPPRESSOR. J. Biol. Chem. 280: 18229-18236 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»