Progerin's 'Discrimination' May Contribute To Fatal Disease That Resembles Premature Aging
The culprit in HGPS, a fatal disease that resembles premature aging, is a protein variant called Progerin. This defective protein impairs cells in many ways, including reducing nuclear levels of the RanGTPase. Ran is crucial for nuclear import and export, as it stimulates unloading of cargo that has just entered the nucleus and loading of cargo that's ready to exit. Progerin also impedes the import of Tpr, which forms the basket-like structure on the inner side of nuclear pores. But the mechanism behind this exclusion wasn't clear.
One possibility is that Progerin disrupts the activity of Tpr's nuclear localization sequence (NLS). To test this idea, a team led by researchers from the University of Virginia replaced Tpr's NLS with the localization sequence from a protein that readily enters the nucleus. The modified Tpr was still locked out, however, suggesting that the effect wasn't related to its NLS.
Tpr is one of the largest proteins to traverse nuclear pores. The researchers found that Progerin also limits the nuclear import of three other hefty proteins. This size effect stems from the reduction in nuclear Ran levels triggered by Progerin. For reasons that are still unclear, large cargoes require more Ran to enter the nucleus. These findings suggest that some cellular defects of HGPS might result from the exclusion of large cargoes, such as multisubunit enzyme complexes, from the nucleus.
Snow, C.J., et al. 2013. J. Cell Biol. doi:10.1083/jcb.201212117
Rockefeller University Press
Source: EurekAlert!, the online, global news service operated by AAAS, the science society
Please use one of the following formats to cite this article in your essay, paper or report:
Rockefeller University Press. "Progerin's 'Discrimination' May Contribute To Fatal Disease That Resembles Premature Aging." Medical News Today. MediLexicon, Intl., 8 May. 2013. Web.
22 Oct. 2016. <http://www.medicalnewstoday.com/releases/260167.php>
Rockefeller University Press. (2013, May 8). "Progerin's 'Discrimination' May Contribute To Fatal Disease That Resembles Premature Aging." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
Contact our news editors
For any corrections of factual information, or to contact our editorial team, please see our contact page.
Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.