來自哈佛醫(yī)學(xué)院細(xì)胞生物學(xué)系,，麻省總醫(yī)院的華裔教授袁鈞英等研究人員在原necroptosis（necrosis + apoptosis,，壞死狀凋亡）研究基礎(chǔ)上,，發(fā)現(xiàn)了一個(gè)調(diào)控壞死狀凋亡的信號(hào)網(wǎng)絡(luò)，以及同時(shí)調(diào)控細(xì)胞凋亡和壞死狀凋亡的分子。這一研究成果公布在12月25日Cell雜志上。
2005年7月,，袁鈞英博士帶領(lǐng)的課題組發(fā)現(xiàn)了一種化學(xué)物質(zhì)Nec-1,它不能對(duì)細(xì)胞調(diào)亡起到抑制作用，它可以對(duì)一種程序性壞死樣細(xì)胞死亡(programmed necrosis-like death)起到特定的抑制作用,。她將之稱為necroptosis（necrosis + apoptosis,，壞死狀凋亡），是一種新的細(xì)胞死亡方式,。袁鈞英一直從事細(xì)胞凋亡的相關(guān)研究,，她的文章數(shù)量少，但是每一篇都是開創(chuàng)性工作，包括早年發(fā)現(xiàn)的caspase家族,，使之成為凋亡研究領(lǐng)域的全球頂尖科學(xué)家,。接下來發(fā)現(xiàn)的壞死性凋亡或稱為非凋亡性程序性死亡,， 同樣具有開創(chuàng)性價(jià)值,。
而在這篇最新的Cell文章中，研究人員主要針對(duì)的是壞死狀凋亡細(xì)胞途徑中的分子信號(hào),，之前的研究發(fā)現(xiàn)像是FasL和TNFα這樣的激動(dòng)劑在存在凋亡環(huán)境的情況下可以激發(fā)凋亡細(xì)胞死亡,，或者缺乏凋亡條件的情況下，利用RIP1激酶促發(fā)細(xì)胞壞死狀凋亡,。
研究人員通過對(duì)壞死狀凋亡調(diào)控因子進(jìn)行全基因組范圍的siRNA篩選,，發(fā)現(xiàn)了432個(gè)調(diào)控壞死狀凋亡的基因，作為RIP1激酶調(diào)控因子（或下游因子）的32個(gè)基因,，細(xì)胞死亡受體介導(dǎo)的細(xì)胞凋亡相關(guān)的32個(gè)基因,， 以及同時(shí)用于壞死狀凋亡和細(xì)胞凋亡的7個(gè)基因。
這432個(gè)基因主要存在于免疫和神經(jīng)系統(tǒng),，并且研究人員還發(fā)現(xiàn)細(xì)胞對(duì)壞死狀凋亡的敏感性受到調(diào)控天然免疫性的一個(gè)廣泛信號(hào)網(wǎng)絡(luò)的調(diào)控,，而且有趣的是，死亡受體介導(dǎo)的壞死狀凋亡需要一個(gè)BH3-only Bcl-2家族成員：Bmf,。
這項(xiàng)研究成果發(fā)現(xiàn)了一個(gè)調(diào)控壞死狀凋亡的信號(hào)網(wǎng)絡(luò),， 以及同時(shí)調(diào)控細(xì)胞凋亡和壞死狀凋亡的分子。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell,26 December 2008 doi:10.1016/j.cell.2008.10.044
Identification of a Molecular Signaling Network that Regulates a Cellular Necrotic Cell Death Pathway
Junichi Hitomi1,Dana E. Christofferson1,3,Aylwin Ng2,3,Jianhua Yao1,Alexei Degterev1,4,Ramnik J. Xavier2andJunying Yuan1,,
1 Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
2 Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114, USA
3 These authors contributed equally to this work
4 Present address: Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
Stimulation of death receptors by agonists such as FasL and TNF activates apoptotic cell death in apoptotic-competent conditions or a type of necrotic cell death dependent on RIP1 kinase, termed necroptosis, in apoptotic-deficient conditions. In a genome-wide siRNA screen for regulators of necroptosis, we identify a set of 432 genes that regulate necroptosis, a subset of 32 genes that act downstream and/or as regulators of RIP1 kinase, 32 genes required for death-receptor-mediated apoptosis, and 7 genes involved in both necroptosis and apoptosis. We show that the expression of subsets of the 432 genes is enriched in the immune and nervous systems, and cellular sensitivity to necroptosis is regulated by an extensive signaling network mediating innate immunity. Interestingly, Bmf, a BH3-only Bcl-2 family member, is required for death-receptor-induced necroptosis. Our study defines a cellular signaling network that regulates necroptosis and the molecular bifurcation that controls apoptosis and necroptosis.
