最近，国际著名科学杂志《自然细胞生物》（Nature Cell Biology）上刊登了北京大学医学部朱卫国教授课题组的重大研究进展：肿瘤抑制因子FoxO1是诱导细胞自噬的关键蛋白，其抗癌作用与其诱导自噬功能密切相关。该论文的第一作者是该实验室的赵颖博士，由北京大学医学部，北京大学人民医院及清华大学相关的研究者共同完成，朱卫国教授是责任作者。
FoxO1 是FOXO家族的重要一员，该蛋白主要调节细胞衰老，细胞周期，代谢及抗肿瘤的作用。传统上认为：FoxO家族蛋白是一类转录因子，通过结合到下游基因启动子而激活一系列重要基因来调节细胞的重要生命过程。朱卫国教授课题组经过多年努力探索，发现FoxO1在细胞浆内起更大作用，即启动另一个重要的生命过程：细胞自噬。他们发现：细胞浆内的FoxO1与组蛋白去乙酰化酶SIRT2结合而保持非活性状态，但在应激情况下FoxO1与SIRT2脱离而变成活化状态的乙酰化FoxO1；该活化状态的FoxO1又特异的结合到一个自噬关键的蛋白ATG7，从而激发了细胞自噬过程。另外，他们从老鼠实验中证实了这种细胞浆内FoxO1引起的自噬是FoxO1抗肿瘤的主要原因之一，同时在临床肿瘤病人标本中也得到了验证。该发现将表观遗传修饰的组蛋白去乙酰化酶与细胞自噬以及肿瘤抑制功能有机的联系起来。（生物谷Bioon.net）
相关研究：
JCB：细胞自噬与膜受体蛋白调控研究
Cell：细胞自噬降解蛋白选择机制
Cell Metabolism：胰腺β细胞自噬与糖尿病的关联
生物谷推荐原文出处：
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.
