最近,，國(guó)際著名科學(xué)雜志《自然細(xì)胞生物》（Nature Cell Biology）上刊登了北京大學(xué)醫(yī)學(xué)部朱衛(wèi)國(guó)教授課題組的重大研究進(jìn)展：腫瘤抑制因子FoxO1是誘導(dǎo)細(xì)胞自噬的關(guān)鍵蛋白，其抗癌作用與其誘導(dǎo)自噬功能密切相關(guān),。該論文的第一作者是該實(shí)驗(yàn)室的趙穎博士，由北京大學(xué)醫(yī)學(xué)部,，北京大學(xué)人民醫(yī)院及清華大學(xué)相關(guān)的研究者共同完成,，朱衛(wèi)國(guó)教授是責(zé)任作者。
FoxO1 是FOXO家族的重要一員,，該蛋白主要調(diào)節(jié)細(xì)胞衰老,，細(xì)胞周期，代謝及抗腫瘤的作用,。傳統(tǒng)上認(rèn)為：FoxO家族蛋白是一類(lèi)轉(zhuǎn)錄因子,，通過(guò)結(jié)合到下游基因啟動(dòng)子而激活一系列重要基因來(lái)調(diào)節(jié)細(xì)胞的重要生命過(guò)程。朱衛(wèi)國(guó)教授課題組經(jīng)過(guò)多年努力探索,，發(fā)現(xiàn)FoxO1在細(xì)胞漿內(nèi)起更大作用,，即啟動(dòng)另一個(gè)重要的生命過(guò)程：細(xì)胞自噬。他們發(fā)現(xiàn)：細(xì)胞漿內(nèi)的FoxO1與組蛋白去乙?；窼IRT2結(jié)合而保持非活性狀態(tài),，但在應(yīng)激情況下FoxO1與SIRT2脫離而變成活化狀態(tài)的乙酰化FoxO1,；該活化狀態(tài)的FoxO1又特異的結(jié)合到一個(gè)自噬關(guān)鍵的蛋白ATG7,，從而激發(fā)了細(xì)胞自噬過(guò)程。另外,，他們從老鼠實(shí)驗(yàn)中證實(shí)了這種細(xì)胞漿內(nèi)FoxO1引起的自噬是FoxO1抗腫瘤的主要原因之一,，同時(shí)在臨床腫瘤病人標(biāo)本中也得到了驗(yàn)證。該發(fā)現(xiàn)將表觀(guān)遺傳修飾的組蛋白去乙?；概c細(xì)胞自噬以及腫瘤抑制功能有機(jī)的聯(lián)系起來(lái),。（生物谷Bioon.net）
相關(guān)研究：
JCB：細(xì)胞自噬與膜受體蛋白調(diào)控研究
Cell：細(xì)胞自噬降解蛋白選擇機(jī)制
Cell Metabolism：胰腺β細(xì)胞自噬與糖尿病的關(guān)聯(lián)
生物谷推薦原文出處：
Nature Cell Biology doi:10.1038/ncb2069
Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity
Ying Zhao1, Jing Yang1, Wenjuan Liao1, Xiangyu Liu1, Hui Zhang1,2, Shan Wang2, Donglai Wang1, Jingnan Feng1, Li Yu3 & Wei-Guo Zhu1,4
Autophagy is characterized by the sequestration of bulk cytoplasm, including damaged proteins and organelles, and delivery of the cargo to lysosomes for degradation. Although the autophagic pathway is also linked to tumour suppression activity, the mechanism is not yet clear. Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation, but this process was independent of the transcriptional activity of FoxO1. In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD+-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death. This FoxO1-modulated cell death is associated with tumour suppressor activity in human colon tumours and a xenograft mouse model. Our finding links the anti-neoplastic activity of FoxO1 and the process of autophagy.
1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
2 Department of Surgery, the Secondary Affiliated Hospital, Peking University Health Science Center, Beijing 100044, China.
3 Department of Biological Science and Biotechnology, Tsinghua University, Beijing 100084, China.
4 School of Oncology, Peking University Health Science Center, Beijing 00142, China.
