The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges
Bibliographic record
Abstract
Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy-rich chains. PolyP is involved in diverse functions in mammalian systems-from cell signaling to blood clotting. One exciting avenue of research is a new nonenzymatic post-translational modification, termed lysine polyphosphorylation, wherein polyP chains are covalently attached to lysine residues of target proteins. While the modification was first characterized in budding yeast, recent work has now identified the first human targets. There is significant promise in this area of biomedical research, but a number of technical issues and knowledge gaps present challenges to rapid progress. In this review, the current state of the field is summarized and existing roadblocks related to the study of lysine polyphosphorylation in higher eukaryotes are introduced. It is discussed how limited methods to identify targets of polyphosphorylation are further impacted by low concentration, unknown regulatory enzymes, and sequestration of polyP into compartments in mammalian systems. Furthermore, suggestions on how these obstacles could be addressed or what their physiological relevance may be within mammalian cells are presented.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".