德國研究人員最新研究發(fā)現(xiàn),，一種細菌毒素可致細胞內(nèi)的一種蛋白失活，致使細胞“自殺”,。這一發(fā)現(xiàn)或有助于研究殺死癌細胞,。相關(guān)論文發(fā)表在近期的《生物化學(xué)雜志》（Journal of Biochemistry）上。
德國弗賴堡大學(xué)8月1日發(fā)表新聞公報說,，該校研究人員發(fā)現(xiàn),，可導(dǎo)致氣性壞疽的產(chǎn)氣莢膜梭菌可產(chǎn)生一種名為“Tpel”的梭菌毒素，這種毒素可將糖分子附著在宿主細胞的Ras蛋白上,，以干擾這種蛋白的自然功能,。
弗賴堡大學(xué)藥理學(xué)家克勞斯·阿克托里斯介紹，人類細胞中的Ras蛋白在激發(fā)細胞生長時發(fā)揮重要作用,，而Tpel毒素則會改變這種蛋白,，讓其無法促進細胞生長,，最終導(dǎo)致細胞死亡。
阿克托里斯說,，人類癌細胞中常出現(xiàn)Ras蛋白的變種,，這種蛋白在癌癥形成中起到重要作用，如果能夠以變種Ras蛋白為靶細胞,，利用這種毒素發(fā)揮作用,，也許能致使癌細胞“自殺”。研究人員目前正在進行進一步研究,。（生物谷Bioon.com）
doi:10.1074/jbc.M112.347773
PMC:
PMID:
Molecular characteristics of Clostridium perfringens TpeL toxin and consequences of mono-O-GlcNAcylation of Ras in living cells
Gregor Guttenberg, Sven Hornei, Thomas Jank, Carsten Schwan, Wei Lü, Oliver Einsle, Panagiotis Papatheodorou and Klaus Aktories*
TpeL is a member of the family of clostridial glucosylating toxins produced by Clostridium perfringens type A, B and C strains. In contrast to other members of this toxin family, it lacks a C-terminal polypeptide repeat domain, which is suggested to be involved in target cell binding. It was shown that the glucosyltransferase domain of TpeL modifies Ras in vitro by mono-O-glucosylation or mono-O-GlcNAcylation (Nagahama, M., Ohkubo, A., Oda, M., Kobayashi, K., Amimoto, K., Miyamoto, K., and Sakurai, J. (2011) Infect. Immun. 79, 905-910). Here we show that TpeL preferably utilizes UDP-N-acetylglucosamine (UDP-GlcNAc) as a sugar donor. Change of alanine-383 of TpeL to isoleucine turns the sugar donor preference from UDP-GlcNAc to UDP-glucose. In contrast to previous studies, we show that Rac is a poor substrate in vitro and in vivo and requires 1-2 magnitudes higher toxin concentrations for modification by TpeL. The toxin is autoproteolytically processed in the presence of inositol hexakisphosphate (InsP6) by an intrinsic cysteine protease domain, located next to the glucosyltransferase domain. A C-terminally extended TpeL full-length variant (TpeL1-1779) induces apoptosis in HeLa cells (most likely by mono-O-GlcNAcylation of Ras), and inhibits Ras signaling including Ras-Raf interaction and ERK activation. In addition, TpeL blocks Ras signaling in rat pheochromocytoma PC12 cells. TpeL is a glucosylating toxin, which modifies Ras and induces apoptosis in target cells without having
