Post-translational Modifications of ATG16L1 are essential for the stability and activation of the Autophagosome Complex
Bibliographic record
Abstract
Autophagy is a cellular stress response pathway that controls cell growth and maintains homeostasis. Dysregulation of autophagy leads to several cytopathic disorders, such as cancer, inflammatory bowel disorders, and neurodegeneration. Cellular stress, such as nutrient starvation or infection, triggers the autophagic cascade by activating the ATG16L1/5-12 protein complex, which delivers cellular compartments to lysosomes for degradation. Very little is known about where ATG16L1 is located under nutrient rich conditions and about the first steps of its activation, prior to binding to nascent autophagosome. We discovered three post-translational modifications (PTM’s) of ATG16L1, S268A, S269/287A, and T281A, that occur under nutrient rich conditions and are lost upon starvation. We also discovered under basal conditions ATG16L1 is localized to the cytoskeleton through interaction with SPEC1L, and that ATG16L1/SPEC1L complex dissociates upon activation. We hypothesize that the stress-sensitive PTM’s mediate the complex’s stability; during stress, they dissociate from the ATG16L1/SPEC1L complex leading to the activation of the complex. My objective is to create phospho-mimetic and phospho-dead mutations of ATG16L1 to detect if these phosphorylation events regulate ATG16L1 inactivation at the cytoskeleton. Mutations were inserted into the genome of virus vectors by Site-Directed Mutagenesis, based on KOD Xtreme Hot Start and Pfu Turbo DNA Polymerase enzymes protocols. Salmonella bacteria were infected with the vectors to evaluate the mutations through direct-sequencing. Mutations will be introduced in vitro into mammalian cells, and the results will be analysed by Western Blotting and Immunoprecipitation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".