Abstract 2037: Investigation into the relationship between intracellular localization of APE1 and cellular stress
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».