Abstract 4048: Aggresome formation is regulated by RanBPM through an interaction with HDAC6.
Bibliographic record
Abstract
Abstract RanBPM (Ran-binding protein M, also called RanBP9) is a nucleocytoplamsic protein that has been implicated in a number of cellular processes including cell adhesion, migration and gene transcription. It has been hypothesized to be a scaffolding protein, but its function remains poorly understood. In previous studies we documented the relocalization of RanBPM from the nucleus to the cytoplasm in response to ionizing radiation (IR) treatment. Subsequent analysis showed that IR triggered cytoplasmic RanBPM relocalization in perinuclear dots or foci often located close to an invagination of the nucleus. Upon further investigation, the RanBPM aggregates were identified as aggresomes, which have not been previously documented to occur in response to IR. Aggresomes are aggregates of misfolded/ubiquitinated proteins resulting from improper protein assembly, aberrant modifications and/or environmental stress. These misfolded/ubiquitinated proteins are normally cleared by chaperone-mediated refolding or by proteasomal degradation through the ubiquitin-proteasome system. In conditions where these systems are impaired or overwhelmed, misfolded proteins accumulate in specific perinuclear structures called aggresome. Further analysis confirmed that the RanBPM foci were indeed aggresomes by assessing co-localization of RanBPM with HDAC6, which is required for aggresome formation. Further, we showed RanBPM also formed aggresome in response to treatment with the proteasome inhibitor MG132. To determine the effect of RanBPM downregulation on aggresome formation, we assessed aggresome formation by HDAC6 in RanBPM shRNA and control shRNA Hela and HEK cells. RanBPM downregulation resulted in significantly lower number of aggresomes both after MG132 and IR treatment, suggesting that RanBPM is essential in aggresome formation. Confocal microscopy analysis showed that RanBPM and HDAC6 co-localize within the aggresome and co-immunoprecipitation studies detected an interaction between the two proteins. Downregulation of RanBPM also resulted in decreased acetylated α-tubulin, suggesting that RanBPM regulates HDAC6 activity. Altogether these results suggest that RanBPM may regulate aggresome formation through an interaction with HDAC6. The molecular details of this regulation are currently under investigation. Citation Format: Louisa Salemi, Ahmad Almawi, Karen Lefebvre, Caroline Schild Poulter. Aggresome formation is regulated by RanBPM through an interaction with HDAC6. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4048. doi:10.1158/1538-7445.AM2013-4048
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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) | 0.003 | 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".