Autofluorescent proteins as photosensitizer in eukaryontes.
Since the discovery of the green fluorescent green protein (GFP) in 1961 many variants of fluorescent proteins (FP) were detected. The importance was underlined by the Nobel price award in chemistry 2008 for the invention, application, and development of the GFP by Shimomura, Chalfie and Tsien. GFP, first described by Shimomura now is indispensible in the scientific daily life. Since then and also in future fluorescent proteins will lead to new applications as reporters in cell biology. Such FPs can absorb visible day-light and predominantly one variant of the red fluorescent protein, the KillerRed protein (KRED) emits active electrons producing reactive oxygen species (ROS) leading to photokilling processes in eukaryotes. KRED can be activated by daylight as a photosensitizing agent. It is quite obvious that the KRED's expression and localization is critical with respect to damage, mutation and finally killing of eukaryotic cells. We found evidence that the KRED's cytotoxicity is ascendantly location-dependent from the cell membrane over the nuclear lamina to the chromatin in the cell nucleus. Daylight illumination of cells harbouring the KRED protein fused with the histone H2A, a DNA-binding protein which is critical for the formation of the chromatin structure results in cell killing. Therefore the H2A-KRED fusion protein can be considered as an appropriate candidate for the photodynamic therapy (PDT). This finding can be transferred to current photodynamic approaches and can enhance their therapeutic outcome.
Waldeck
Waldemar
W
German Cancer Research Center, Department of Biophysics of Macromolecules, Heidelberg, Germany.
Mueller
Gabriele
G
Wiessler
Manfred
M
Brom
Manuela
M
Tóth
Katalin
K
Braun
Klaus
K
D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D009369:Neoplasms / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014162:Transfection
D017319:Photosensitizing Agents; D011993:Recombinant Fusion Proteins; C508771:killer red protein, Anthomedusae; D049452:Green Fluorescent Proteins