ULK1·ATG13·FIP200 complex mediates mTOR signaling and is essential for autophagy Journal Article
| Authors: | Ganley, I. G.; Lam, D. H.; Wang, J.; Ding, X.; Chen, S.; Jiang, X. |
| Article Title: | ULK1·ATG13·FIP200 complex mediates mTOR signaling and is essential for autophagy |
| Abstract: | Autophagy is a degradative process that recycles long-lived and faulty cellular components. It is linked to many diseases and is required for normal development. ULK1, a mammalian serine/threonine protein kinase, plays a key role in the initial stages of autophagy, though the exact molecular mechanism is unknown. Here we report identification of a novel protein complex containing ULK1 and two additional protein factors, FIP200 and ATG13, all of which are essential for starvation-induced autophagy. Both FIP200 and ATG13 are critical for correct localization of ULK1 to the pre-autophagosome and stability of ULK1 protein. Additionally, we demonstrate by using both cellular experiments and a de novo in vitro reconstituted reaction that FIP200 and ATG13 can enhance ULK1 kinase activity individually but both are required for maximal stimulation. Further, we show that ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1 center dot ATG13 center dot FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis. |
| Keywords: | autophagy; autophagosome biogenesis |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 284 |
| Issue: | 18 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2009-05-01 |
| Start Page: | 12297 |
| End Page: | 12305 |
| Language: | English |
| ACCESSION: | BIOSIS:PREV200900358672 |
| DOI: | 10.1074/jbc.M900573200 |
| PROVIDER: | biosis |
| PMCID: | PMC2673298 |
| PUBMED: | 19258318 |
| Notes: | --- - Article - "Source: Biosis" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work