Enforced expression of PPP1R13L increases tumorigenesis and invasion through p53-dependent and p53-independent mechanisms.
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- Institute of Human Genetics, University of Aarhus, Aarhus, Denmark
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
- Department for Toxicology and Risk Assessment, National Food Institute, Søborg, Denmark
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- Manuscript
- Date:
- Received 24 June 2008 16:03 UTC; Posted 24 June 2008
- Subjects:
- Cancer
- Abstract:
PPP1R13L was initially identified as a protein that binds to the NF-κB subunit p65/RelA and inhibits its transcriptional activity. It also binds p53 and inhibits its action. One set of experimental findings based on over-expression of PPP1R13L indicates that PPP1R13L blocks apoptosis. Another set of experiments, based on endogenous production of PPP1R13L, suggests that the protein may sometimes be pro-apoptotic. We have used primary mouse embryonic fibroblasts (MEFs), dually transformed by H-ras and Adenovirus E1A and differing in their p53 status, to explore the effects of PPP1R13L over-expression, thus examining the ability of PPP1R13L to act as an oncoprotein. We found that over-expression of PPP1R13L strongly accelerated tumor formation by ras/E1A and also resulted in an increased metastatic potential of the tumors. PPP1R13L over-expressing cells were depleted for both p53 and active p65/RelA and we found that both p53 dependent and independent apoptosis pathways were regulated by PPP1R13L. Finally, studies with the proteasome inhibitor MG132 revealed that over-expression of PPP1R13L causes faster p53 degradation, a likely explanation for the depletion of p53. Taken together, our results show that increased levels of PPP1R13L can increase tumorigenesis and furthermore pinpoint PPP1R13L as a gene that influences metastasis.
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- This document is licensed to the public under the Creative Commons Attribution 3.0 License
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Laska, Magdalena, Lowe, Scott, Zender, Lars, Hearn, Stephen, Vogel, Ulla, Jensen, Uffe Birk, Bric, Anka, and Nexø, Bjørn. Enforced expression of PPP1R13L increases tumorigenesis and invasion through p53-dependent and p53-independent mechanisms.. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.2004.1> (2008)
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