Abstract 2037: Investigation into the relationship between intracellular localization of APE1 and cellular stress
Bibliographic record
Abstract
Abstract Apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor (Ref-1) is a key regulator of cellular response to oxidative stress. It is a multifunctional protein involved in both transcriptional regulation of gene expression during adaptive cellular response to oxidative stress, and in base excision repair pathway of DNA lesions generated as a consequence of oxidant-induced base damages. In the latter, APE1/Ref-1 contributes to the maintenance of the genome stability. APE1 normally resides in the nucleus and this is consistent with its established role in base excision repair and redox regulation of transcription factors [Tell et al 2009]. However, in some cancers, abnormal re-distribution of APE1 to the cytoplasm or its presence in both the nucleus and the cytoplasm without losing its ability to repair abasic DNA has been observed and these have baffled many researchers [Tell et al 2005]. We have recently identified APE1/Ref-1 as an endoribonuclease that cleaves c-myc mRNA in vitro and influence the steady-state c-myc mRNA as well as its half-life in HeLa cells [Barnes et al 2009]. It is currently unknown if the re-distribution of APE1 to cytoplasm in cancer is coupled and related to its RNA-cleaving function in cells. To address this question and to understand the role of cytoplasmic APE1, we have generated plasmids encoding fusion green fluorescent protein and wild-type APE1 (GFP-APE1), as well as N-terminus deleted form of APE1 (GFP-ND20 APE1 and GFP-ND41 APE1). The fusion proteins were expressed in HeLa cells and examined using confocal microscopy. Our results showed that the wild-type APE1 is exclusively located in the nucleus. However, upon deletion at the N-terminus, APE1 is re-distributed to both the nucleus and the cytoplasm. To determine if APE1 can re-localize to the processing bodies (PBs) and stress granules (SGs), which are cytoplasmic locales where mRNAs are degraded, we co-expressed cells with Dcp1a-RFP or TIA-1-RFP. Our results showed that the wild-type and N-terminus deleted form of APE1 did not co-localize to PBs and SGs in HeLa cells. To determine if APE1 can re-localize to the PBs and SGs under cellular stress, we treated cells with S-nitrosoglutathione which induces nitrosative stress, and sodium arsenite which induces oxidative stress. Our results showed that neither the wild-type nor N-terminus deleted form of APE1are localize to the PBs and SGs upon cellular stress in HeLa cells. These results suggest that APE1 is not likely to play any significant role in degrading RNA upon cellular stress in HeLa cells. We have also investigated the possible link between the cellular localization of APE1 and its RNA-cleaving function in other cell types, and the results will be presented and discussed. Understanding the cytoplasmic role of APE1 is expected to provide clues as to why APE1 is re-distributed to the cytoplasm in some cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2037. doi:10.1158/1538-7445.AM2011-2037
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".