Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34239
Mueller, A; Schäfer, B W; Ferrari, S; Weibel, M; Makek, M; Höchli, M; Heizmann, C W (2005). The calcium-binding protein S100A2 interacts with p53 and modulates its transcriptional activity. Journal of Biological Chemistry, 280(32):29186-29193.
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Head and neck squamous cell carcinoma express high levels of the EF-hand calcium-binding protein S100A2 in contrast to other tumorigenic tissues and cell lines where the expression of this protein is reduced. Subtractive hybridization of tumorigenic versus normal tumor-derived mammary epithelial cells has previously identified the S100A2 protein as potential tumor suppressor. The biological function of S100A2 in carcinogenesis, however, has not been elucidated to date. Here, we report for the first time that during recovery from hydroxyurea treatment, the S100A2 protein translocated from the cytoplasm to the nucleus and co-localized with the tumor suppressor p53 in two different oral carcinoma cells (FADU and SCC-25). Co-immunoprecipitation experiments and electrophoretic mobility shift assay showed that the interaction between S100A2 and p53 is Ca(2+)-dependent. Preliminary characterization of this interaction indicated that the region in p53 involved with binding to S100A2 is located at the C terminus of p53. Finally, luciferase-coupled transactivation assays, where a p53-reporter construct was used, indicated that interaction with S100A2 increased p53 transcriptional activity. Our data suggest that in oral cancer cells the Ca(2+)- and cell cycle-dependent p53-S100A2 interaction might modulate proliferation.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research|
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Deposited On:||09 Jul 2010 14:31|
|Last Modified:||02 Dec 2013 01:20|
|Publisher:||American Society for Biochemistry and Molecular Biology|
|Free access at:||Publisher DOI. An embargo period may apply.|
|Citations:||Web of Science®. Times cited: 69|
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