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Pernille Winding

Publications and source records attributed to Pernille Winding.

2 recordsLinked to original sources

ALG-2, a multifunctional calcium binding protein?

ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article discusses the current knowledge on the structure and potential function of this protein. Several putative binding partners of ALG-2 have been identified hinting to functions of ALG-2 in apoptosis and possibly also in proliferation, endocytosis and transcriptional regulation during development. Gene deletion of the well conserved ALG-2 locus in several genetic model organisms has so far not provided insights into functions and signaling pathways with ALG-2 involvement. Special focus is given to controversial data on expression and localization of ALG-2, which is mainly caused by the use of ALG-2 antibodies with different specificities.

Animals↗

Up-regulation of ALG-2 in hepatomas and lung cancer tissue.

ALG-2 was isolated in a screen for proteins involved in programmed cell death and is the first Ca(2+)-binding protein found to be directly involved in apoptosis. We have generated polyclonal antibodies that are suitable for detecting ALG-2 using different immunological methods. Three commercial antibodies against ALG-2 did neither detect mouse recombinant ALG-2 nor endogenous ALG-2 in Jurkat cell lysates, whereas our own affinity-purified antibody recognized recombinant as well as endogenous ALG-2. The specificity of the antibody was shown by preabsorbtion experiments and on ALG-2-deficient cells using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our results lead to the conclusion that ALG-2 beside its known proapoptotic functions may be a player in survival pathways.

Animals↗