軍事醫(yī)學科學院蛋白質(zhì)組學國家重點實驗室在中科院院士賀福初的帶領(lǐng)下，張令強副研究員課題組在骨骼形成研究領(lǐng)域又有重要新發(fā)現(xiàn)：骨頭形成的負調(diào)控基因在骨頭穩(wěn)定狀態(tài)調(diào)控中的作用機制。為骨質(zhì)疏松病的預(yù)防,、診斷,、治療提供了新的靶點。這一研究成果發(fā)表于7月20日出版的國際著名學術(shù)刊物——《自然—細胞生物學》（Nature Cell Biology） ,。
賀福初院士和他的學生張令強副研究員帶領(lǐng)課題組通過與該院生物工程研究所楊曉研究員合作,，利用生物技術(shù)手段剔除小鼠體內(nèi)的負調(diào)控基因，然后與正常的小鼠進行比較,，意外發(fā)現(xiàn)剔除負調(diào)控基因的小鼠整體骨頭的重量明顯升高,、骨頭的功能明顯增強，而且年齡越老的小鼠骨頭的重量變化越明顯,。這一變化充分證明了這種基因在骨頭形成過程中起著重要的負調(diào)控作用,，并成為國際上第一個關(guān)于此基因功能的遺傳學證據(jù)。他們進一步研究還發(fā)現(xiàn),，這種負調(diào)控基因可以增強骨頭形成的另一種重要蛋白分子的活性。這種蛋白分子可以在參與骨形成的關(guān)鍵蛋白質(zhì)上添加一串信號,。這個信號可以被蛋白質(zhì)降解機器識別,，從而將蛋白質(zhì)剪切為肽段，又發(fā)現(xiàn)這種蛋白分子發(fā)揮功能需要依賴負調(diào)控基因的輔助激活作用,，在負調(diào)控基因缺失的小鼠體內(nèi)這種蛋白分子的活性大大降低,，骨重塑的平衡狀態(tài)被打破，而負調(diào)控基因的存在則可以幫助這種蛋白分子更好地識別并結(jié)合它要修飾并降解的蛋白分子,。
賀福初介紹,，“蛋白質(zhì)組學國家重點實驗室今年在英國《自然》系列刊物已發(fā)表了3篇論文。這個實驗室是目前我國在蛋白質(zhì)組學領(lǐng)域批準建立的唯一國家重點實驗室,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology,，doi:10.1038/ncb1760，Kefeng Lu, Lingqiang Zhang & Fuchu He
Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1
Kefeng Lu1,4, Xiushan Yin1,4, Tujun Weng2, Shenli Xi1, Li Li1, Guichun Xing1, Xuan Cheng2, Xiao Yang2, Lingqiang Zhang1 & Fuchu He1,3
E3 ubiquitin ligases are final effectors of the enzyme cascade controlling ubiquitylation1. A central issue in understanding their regulation is to decipher mechanisms of their assembly and activity2. In contrast with RING-type E3s, fewer mechanisms are known for regulation of HECT-type E3s2, 3, 4. Smad ubiquitylation regulatory factor 1 (Smurf1), a C2-WW-HECT-domain E3, is crucial for bone homeostasis, in which it suppresses osteoblast activity5, 6. However, whether and how its activity is regulated remains unclear. Here we show that Smurf1, but not Smurf2, interacts with casein kinase-2 interacting protein-1 (CKIP-1), resulting in an increase in its E3 ligase activity. Surprisingly, CKIP-1 targets specifically the linker region between the WW domains of Smurf1, thereby augmenting its affinity for and promoting ubiquitylation of the substrate. Moreover, CKIP-1-deficient mice undergo an age-dependent increase in bone mass as a result of accelerated osteogenesis and decreased Smurf1 activity. These findings provide evidence that the WW domains linker is important in complex assembly and in regulating activity of HECT-type E3s and that CKIP-1 functions as the first auxiliary factor to enhance the activation of Smurf1.
