加拿大研究人員發(fā)現(xiàn)了一種能夠調(diào)節(jié)細(xì)胞凋亡機(jī)制的蛋白質(zhì),，該新發(fā)現(xiàn)對(duì)癌癥的診斷和治療都將產(chǎn)生影響,。此項(xiàng)研究成果發(fā)表在《分子癌癥研究》雜志的網(wǎng)絡(luò)版上。
該項(xiàng)目研究人員,、西安大略大學(xué)羅伯茲癌癥研究所的卡羅琳·席爾德-保爾特解釋道,，鑒別出的蛋白質(zhì)RanBPM可直接參與激活細(xì)胞凋亡。癌癥的主要特點(diǎn)之一是,，細(xì)胞盡管在其遺傳物質(zhì)中有缺陷,，但細(xì)胞并不主動(dòng)凋亡,。換句話說(shuō)，受損細(xì)胞不能確保會(huì)自殺,，從而發(fā)展成癌癥,。無(wú)法激活細(xì)胞凋亡也造成了癌癥治療的難點(diǎn)。由于這些細(xì)胞抵御死亡,，因此也就無(wú)法用化療或放療方法引發(fā)DNA損傷來(lái)殺死這些細(xì)胞,。
席爾德-保爾特表示，雖然還需要進(jìn)行更多的研究來(lái)充分了解這些蛋白的功能,，但RanBPM能成為重新激活細(xì)胞凋亡,、殺死癌細(xì)胞的靶標(biāo)。此蛋白也可成為預(yù)測(cè)腫瘤是否會(huì)發(fā)展為惡性的一個(gè)標(biāo)記,。（生物谷Bioon.com）
生物谷推薦原始出處：
molecular cancer research December 2009; doi: 10.1158/1541-7786.MCR-09-0098
RanBPM Has Proapoptotic Activities That Regulate Cell Death Pathways in Response to DNA Damage
Elnaz Atabakhsh1,2, Dawn M. Bryce1, Karen J. Lefebvre2 and Caroline Schild-Poulter1,2
1Robarts Research Institute and 2Department of Biochemistry, The University of Western Ontario, London, Ontario, Canada
Ran-binding protein M (RanBPM) is a nucleocytoplasmic protein previously implicated in various signaling pathways, but whose function remains enigmatic. Here, we provide evidence that RanBPM functions as an activator of apoptotic pathways induced by DNA damage. First, transient expression of RanBPM in HeLa cells induced cell death through caspase activation, and in the long-term, forced expression of RanBPM impaired cell viability. RanBPM COOH-terminal domain stimulated the ability of RanBPM to induce caspase activation, whereas this activity was negatively regulated by the central SPRY domain. Second, small interfering RNA–directed knockdown of RanBPM prevented DNA damage–induced apoptosis, as evidenced by the marked reduction in caspase-3 and caspase-2 activation. This correlated with a magnitude fold increase in the survival of RanBPM-depleted cells. Following ionizing radiation treatment, we observed a progressive relocalization of RanBPM from the nucleus to the cytoplasm, suggesting that the activation of apoptotic pathways by RanBPM in response to ionizing radiation may be regulated by nucleocytoplasmic trafficking. Finally, RanBPM downregulation was associated with a marked decrease of mitochondria-associated Bax, whereas Bcl-2 overall levels were dramatically upregulated. Overall, our results reveal a novel proapoptotic function for RanBPM in DNA damage–induced apoptosis through the regulation of factors involved in the mitochondrial apoptotic pathway.
