Abstract 4389: Post-translational modifications of histone demethylase JMJD1A in prostate cancer cells
Bibliographic record
Abstract
Abstract Castration-resistant prostate cancer (CRPC) is the major cause of death for prostate cancer (PCa) patients. Re-activation of androgen receptor (AR) activity during androgen-deprivation therapy is believed to underlie CRPC development. We have found that histone demethylase JMJD1A primarily regulates AR and c-Myc activity and thus plays a key role in promoting PCa cell proliferation or survival. Unfortunately, specific JMJD1A inhibitors are not yet available. Here, we identified several post-translational modifications of JMJD1A by performing the JMJD1A immunoprecipitation and mass spectrometry analysis. These modifications include the canonical ubiquitination that targets JMJD1A for proteasome-dependent degradation, non-canonical ubiquitination that enhances the recruitment of co-activators, as well as those that can regulate these ubiquitination events. We also found that these modifications could be manipulated by commercially available inhibitors, to reduce the JMJD1A protein level and prostate cancer cell growth. Thus, targeting the JMJD1A modifications may serve as an alternative means to inhibit JMJD1A activity for the anti-PCa therapy. Note: This abstract was not presented at the meeting. Citation Format: Songhui Xu, Lingling Fan, Xiaolu Cui, Fengbo Zhang, Arif Hussain, Ladan Fazli, Martin Gleave, Jianfei Qi. Post-translational modifications of histone demethylase JMJD1A in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4389.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".