2. SUMO1-CDK6 conjugation drives the cell cycle and retains the self renewal of glioblastoma stem cells
Bibliographic record
Abstract
The current concept in the cell cycle stipulates that constant synthesis without coupled ubiquitin- mediated proteolysis maintains the levels of cyclin-dependent kinase proteins through the cell cycle. CDK proteins are elevated in glioblastoma, which has long been thought due to gene amplifications, although the amplifications occur only in a small set of the tumors according to the genome. In this study, we show that the G1 phase CDK6 is a substrate of both ubiquitin and small ubiquitin-like modifier-1 (SUMO1), and that CDK6 is sumoylated due to the elevated activity of SUMO1 conjugation in glioblastoma. CDK6 sumoylation at Lys 216 structurally blocks the access of ubiquitination molecules to the Lys 147 ubiquitination site; thus, CDK6 sumoylation stabilize the protein, maintains the kinase activity and drives the cell cycle through G1/S transition. Inhibition of SUMO1 conjugation causes G1 arrest and abolishes the self-renewal and tumorigenic property of glioblastoma initiating or stem cells. In conclusion, SUMO1-CDK6 conjugation constitutes a new mechanism of cell cycle control and selective inhibition of SUMO1 conjugation may provide a novel strategy for the development of the cancer stem cells-targeted treatment.
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 | 0.000 | 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) | 0.002 | 0.000 |
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".