近日,，中科院微生物所百人計劃引進人才葉昕研究員課題組通過研究，發(fā)現(xiàn)了與細胞周期調(diào)控的關(guān)鍵調(diào)控分子Cyclins/Cdks新相互作用蛋白－錨蛋白Ankrd17,，研究結(jié)果發(fā)表在Journal of Biological Chemistry 284期第12卷上,。
細胞周期在細胞的生長，分化及分裂過程中扮演著極其重要的角色,，細胞周期的失控伴隨著腫瘤的發(fā)生或細胞的凋亡,。Cyclins/Cdks蛋白激酶為細胞周期調(diào)控最為關(guān)鍵的調(diào)控分子，其中CyclinE/Cdk2在細胞周期的G1/S檢驗點轉(zhuǎn)換過程中發(fā)揮著極其關(guān)鍵的作用,。目前已經(jīng)發(fā)現(xiàn)了一些與CyclinE/Cdk2相互作用的蛋白參與細胞周期的調(diào)控,，但是CyclinE/Cdk2調(diào)控細胞周期的詳盡的信號轉(zhuǎn)導網(wǎng)絡尚未明晰。
為了進一步闡明CyclinE/Cdk2在細胞周期G1/S檢驗點的功能,，我所葉昕研究員課題組的博士研究生鄧敏和李發(fā)慧,，通過TAP親和純化技術(shù)篩選到CyclinE/Cdk2新相互作用蛋白－錨蛋白Ankrd17，并對Ankrd17調(diào)控細胞周期的機理進行系統(tǒng)的研究,，這在國際上尚屬首次,。該研究通過體外激酶反應及質(zhì)譜分析等手段，證實Ankrd17為Cyclin E/Cdk2的底物,，并定位其磷酸化位點; 通過免疫熒光染色,、RNAi干擾及流式細胞術(shù)等方法發(fā)現(xiàn)Ankrd17能促進細胞周期的進行, 同時發(fā)現(xiàn)Ankrd17通過調(diào)控DNA復制相關(guān)蛋白Cdc6和PCNA與DNA的結(jié)合而參與DNA復制; 研究結(jié)果表明Ankrd17是細胞周期G1/S期轉(zhuǎn)換過程中的一種正調(diào)控蛋白,。
該項研究結(jié)果有助于進一步理解CyclinE/Cdk2激酶復合體在細胞周期調(diào)控及腫瘤發(fā)生過程中的作用，進而為尋找新的抗腫瘤治療靶標提供理論依據(jù),。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Biol. Chem., Vol. 284, Issue 12, 7875-7888, March 20, 2009
Min Deng1, Fahui Li1, Bryan A. Ballif?2, Shan Li||, Xi Chen**, Lin Guo**, and Xin Ye3
From the Department of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China, the ?Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, the ||Shandong Normal University, Jinan, Shandong 250014, China, the **College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China, and the Graduate University of Chinese Academy of Sciences, Beijing 100101, China
Cyclin E/Cdk2 is a key regulator in G1-S transition. We have identified a novel cyclin E/Cdk2 substrate called Ankrd17 (ankyrin repeat protein 17) using the TAP tag purification technique. Ankrd17 protein contains two clusters of a total 25 ankyrin repeats at its N terminus, one NES (nuclear exporting signal) and one NLS (nuclear localization signal) in the middle, and one RXL motif at its C terminus. Ankrd17 is expressed in various tissues and associates with cyclin E/Cdk2 in an RXL-dependent manner. It can be phosphorylated by cyclin E/Cdk2 at 3 phosphorylation sites (Ser1791, Ser1794, and Ser2150). Overexpression of Ankrd17 promotes S phase entry, whereas depletion of Ankrd17 expression by small interfering RNA inhibits DNA replication and blocks cell cycle progression as well as up-regulates the expression of p53 and p21. Ankrd17 is localized to the nucleus and interacts with DNA replication factors including MCM family members, Cdc6 and PCNA. Depletion of Ankrd17 results in decreased loading of Cdc6 and PCNA onto DNA suggesting that Ankrd17 may be directly involved in the DNA replication process. Taken together, these data indicate that Ankrd17 is an important downstream effector of cyclin E/Cdk2 and positively regulates G1/S transition.
