Hara Taichi, Mizushima Noboru
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Autophagy. 2009 Jan;5(1):85-7. doi: 10.4161/auto.5.1.7180. Epub 2009 Jan 13.
The yeast serine threonine kinase Atg1 appears to be a key regulator of autophagy and its kinase activity is crucial for autophagy induction. Recent reports have indicated that a mammalian Atg1 homolog, UNC-51-like kinase (ULK) 1, is required for autophagy. We found that ULK1 localizes to the autophagic isolation membrane and its kinase activity is important for autophagy induction. Furthermore, we identified a focal adhesion kinase (FAK) family interacting protein of 200 kD (FIP200) as a ULK-interacting protein. FIP200 also localizes to the isolation membrane together with ULK. Using FIP200-deficient cells, we found that FIP200 is essential for autophagosome formation and the proper function of ULK. Here, we discuss the role of the ULK-FIP200 complex in autophagy and the possibility that FIP200 functions as a mammalian counterpart of Atg17.
酵母丝氨酸苏氨酸激酶Atg1似乎是自噬的关键调节因子,其激酶活性对于自噬诱导至关重要。最近的报道表明,一种哺乳动物Atg1同源物,UNC-51样激酶(ULK)1,是自噬所必需的。我们发现ULK1定位于自噬隔离膜,其激酶活性对于自噬诱导很重要。此外,我们鉴定出一种200kD的粘着斑激酶(FAK)家族相互作用蛋白(FIP200)作为ULK相互作用蛋白。FIP200也与ULK一起定位于隔离膜。使用FIP200缺陷细胞,我们发现FIP200对于自噬体形成和ULK的正常功能至关重要。在此,我们讨论ULK-FIP200复合物在自噬中的作用以及FIP200作为Atg17的哺乳动物对应物发挥作用的可能性。