Abstract:
:In a recent screening for genes down regulated in replicatively senescent human umbilical vein endothelial cells (HUVECs), we have isolated the novel protein SNEV. Since then SNEV has proven as a multifaceted protein playing a role in pre-mRNA splicing, DNA repair, and the ubiquitin/proteosome system. Here, we report that SNEV mRNA decreases in various cell types during replicative senescence, and that it is increased in various immortalized cell lines, as well as in breast tumors, where SNEV transcript levels also correlate with the survival of breast cancer patients. Since these mRNA profiles suggested a role of SNEV in the regulation of cell proliferation, the effect of its overexpression was tested. Thereby, a significant extension of the cellular life span was observed, which was not caused by altered telomerase activity or telomere dynamics but rather by enhanced stress resistance. When SNEV overexpressing cells were treated with bleomycin or bleomycin combined with BSO, inducing DNA damage as well as reactive oxygen species, a significantly lower fraction of apoptotic cells was found in comparison to vector control cells. These data suggest that high levels of SNEV might extend the cellular life span by increasing the resistance to stress or by improving the DNA repair capacity of the cells.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Voglauer R,Chang MW,Dampier B,Wieser M,Baumann K,Sterovsky T,Schreiber M,Katinger H,Grillari Jdoi
10.1016/j.yexcr.2005.11.025keywords:
subject
Has Abstractpub_date
2006-04-01 00:00:00pages
746-59issue
6eissn
0014-4827issn
1090-2422pii
S0014-4827(05)00560-4journal_volume
312pub_type
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