瑞典科學(xué)家近日研究發(fā)現(xiàn)了一種細(xì)胞生長(zhǎng)因子的全新信號(hào)通道,，這種生長(zhǎng)因子對(duì)于癌細(xì)胞的存活和生長(zhǎng)至關(guān)重要,。這一發(fā)現(xiàn)為某些癌癥的研究開(kāi)啟了全新的圖景。相關(guān)論文8月31日在線發(fā)表于《自然—細(xì)胞生物學(xué)》（Nature Cell Biology）上,。
人體細(xì)胞“理解”來(lái)自多種生長(zhǎng)因子的信號(hào)的能力,，對(duì)于正常的胎兒發(fā)育極為重要。癌細(xì)胞的入侵性和存活能力同樣由許多生長(zhǎng)因子控制,，其中轉(zhuǎn)化生長(zhǎng)因子b（TGF-b）發(fā)揮著顯著作用,。
在最新的研究中，瑞典烏普薩拉大學(xué)遺傳學(xué)與病理學(xué)系的Marene Landstr?m和同事發(fā)現(xiàn)了一個(gè)全新的由TGF-b調(diào)控的信號(hào)通道,。Landstr?m說(shuō)：“這一發(fā)現(xiàn)具有重大的價(jià)值,，它可以幫助我們鑒別TGF-b使用何種信號(hào)通道來(lái)抑制細(xì)胞生長(zhǎng)，以及刺激癌細(xì)胞存活和轉(zhuǎn)移的能力,。”
TGF-b通過(guò)綁定在細(xì)胞膜上的受體將信號(hào)傳入細(xì)胞內(nèi),，與大多數(shù)動(dòng)物中的方式類(lèi)似。大約十年前,，科學(xué)家發(fā)現(xiàn)了所謂的Smad蛋白,，它是活躍TGF-b信號(hào)的獨(dú)特信使,。當(dāng)磷酸鹽綁定于其上時(shí)，這些蛋白會(huì)被激活,，激活的方式依賴(lài)于TGF-b受體內(nèi)酶（絲氨酸-蘇氨酸激酶）的活性,。
而新發(fā)現(xiàn)的信號(hào)通道完全不依賴(lài)于絲氨酸-蘇氨酸激酶活性。研究顯示,，另外一種酶——TRAF6被激活,，它綁定在受體聯(lián)合體上。TRAF6是一個(gè)泛素連接酶（ubiquitin-ligase）,，當(dāng)它被激活的時(shí)候,，會(huì)在自身和其它蛋白上產(chǎn)生短小蛋白鏈。因此TRAF6作為一個(gè)開(kāi)關(guān),，能夠決定在細(xì)胞內(nèi)開(kāi)啟何種信號(hào),。TGF-利用TRAF6特定地激活激酶TAK1，TAK1隨后激活其它的應(yīng)激活化激酶,，導(dǎo)致細(xì)胞死亡,。
研究人員表示，“發(fā)現(xiàn)TGF-利用TRAF6激活細(xì)胞內(nèi)信號(hào)通道，為未來(lái)的研究開(kāi)啟了全新的圖景,。這使得開(kāi)發(fā)新的治療策略來(lái)對(duì)抗一些依賴(lài)TGF-的晚期癌癥成為可能,，如乳腺癌和前列腺癌。”（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology,，doi:10.1038/ncb1780,，Alessandro Sorrentino，Maréne Landstr?m
The type I TGF- receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
Alessandro Sorrentino1,3, Noopur Thakur1,2,3, Susanne Grimsby1,3, Anders Marcusson1,2, Verena von Bulow1, Norbert Schuster1, Shouting Zhang1, Carl-Henrik Heldin1 & Maréne Landström1,2
Transforming growth factor- (TGF-) is a multifunctional cytokine that regulates embryonic development and tissue homeostasis; however, aberrations of its activity occur in cancer1, 2. TGF- signals through its Type II and Type I receptors (TRII and TRI) causing phosphorylation of Smad proteins3, 4. TGF--associated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, was originally identified as an effector of TGF--induced p38 activation5. However, the molecular mechanisms for its activation are unknown. Here we report that the ubiquitin ligase (E3) TRAF6 interacts with a consensus motif present in TRI. The TRI–TRAF6 interaction is required for TGF--induced autoubiquitylation of TRAF6 and subsequent activation of the TAK1–p38/JNK pathway, which leads to apoptosis. TRI kinase activity is required for activation of the canonical Smad pathway, whereas E3 activity of TRAF6 regulates the activation of TAK1 in a receptor kinase-independent manner. Intriguingly, TGF--induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF- specifically activates TAK1 through interaction of TRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6.
