The SUMO Conjugating Enzyme Ubc9 Is Required for Inducing and Maintaining Stem Cell Pluripotency
Bibliographic record
Abstract
Sumoylation adds a small ubiquitin-like modifier (SUMO) polypeptide to the ε-amino group of a lysine residue. Reminiscent of ubiquitination, sumoylation is catalyzed by an enzymatic cascade composed of E1, E2, and E3. For sumoylation, this cascade uses Ubc9 (ubiquitin conjugating enzyme 9, now officially named ubiquitin conjugating enzyme E2I [UBE2I]) as the sole E2 enzyme. Here, we report that expression of endogenous Ubc9 increases during reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. In addition, this E2 enzyme is required for reprogramming as its suppression dramatically inhibits iPS cell induction. While Ubc9 knockdown does not affect survival of MEFs and immortalized fibroblasts, Ubc9 is essential for embryonic stem cell (ESC) survival. In addition, we have found that Ubc9 knockdown stimulates apoptosis in ESCs but not in MEFs. Furthermore, the knockdown decreases the expression of the well-known pluripotency marker Nanog and the classical reprogramming factors Klf4, Oct4, and Sox2 in ESCs. Together, these observations indicate that while dispensable for fibroblast survival, the sole SUMO E2 enzyme Ubc9 plays a critical role in reprogramming fibroblasts to iPS cells and maintaining ESC pluripotency.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 | 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) | 0.000 | 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 teacher head, 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".