siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy
What this study shows
The authors screened a kinase-targeted siRNA library in human HEK293 cells, using lipidation of the autophagy marker GFP-LC3 after amino-acid starvation as the readout. ULK1 came out of the screen: knocking it down blocked starvation-induced autophagy, while knocking down the related kinase ULK2 did not. ULK1 knockdown also blocked autophagy induced by rapamycin, which fits ULK1 acting downstream of mTOR. Overexpressed ULK1 inhibited autophagy independently of its kinase activity, and the dominant-negative effect mapped to residues 1-351, while the conserved C-terminal domain was needed for ULK1 to reach cytoplasmic structures, some of them LC3-positive. One of the early papers to place ULK1 as a required kinase for starvation-induced autophagy in mammalian cells. Boundary: Cultured human cell lines with siRNA and overexpression; no whole-animal data. The link to mTOR rests on rapamycin-induced autophagy, not on a measurement of mTORC1 acting on ULK1. Drafted from the abstract only (no PMC full text).
At a glance
| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: HEK293 cells (GFP-LC3 lipidation assay, kinome siRNA library); HeLa cells; rat ULK1 constructs) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | HEK293 cells (GFP-LC3 lipidation assay, kinome siRNA library); HeLa cells; rat ULK1 constructs |
| Journal | Journal of Biological Chemistry |
| Year | 2007 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1074/jbc.m703663200 · PMID 17595159 |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | siRNA knockdown of ULK1 (kinome screen); ULK1 overexpression and deletion mutants; amino-acid starvation or rapamycin to induce autophagy |
| Target | ULK1 |
| Model | Human cells (HEK293, HeLa) |
| Effect | ULK1 knockdown decreased starvation- and rapamycin-induced autophagy (GFP-LC3 lipidation); ULK2 knockdown did not |
In the Atlas
Related topics
Links in the pathway map
- Supports ULK1 activates Autophagy
More studies on this topic
- Reduced dietary protein intake does not alter autophagy in human blood: A randomized crossover study in healthy adults (2026)
- Testosterone propionate maintains autophagic flux and mitochondrial integrity via regulation of the LC3B/p62/Beclin-1/mTOR axis in induced liver fibrosis. (2026)
- NUFIP1 is a ribosome receptor for starvation-induced ribophagy (2018)
- A systems study reveals concurrent activation of AMPK and mTOR by amino acids (2016)
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