التفاصيل البيبلوغرافية
| العنوان: |
Data from HuR-Mediated Control of C/EBPβ mRNA Stability and Translation in ALK-Positive Anaplastic Large Cell Lymphomas |
| المؤلفون: |
Estelle Espinos, Dominique Morello, Georges Delsol, Laurence Lamant, Cecile Desjobert, Celine Lopez, Mohamad Fawal, Julie Bergalet |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
The CCAAT/enhancer-binding protein β (C/EBPβ) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK+). Although ALK-mediated C/EBPβ transcriptional activation has been reported, C/EBPβ mRNA possesses U- and AU-rich domains in its 3′-untranslated region (3′-UTR) that might be privileged targets for posttranscriptional control in ALK+ ALCLs. The purpose of this study was to explore this possibility. By using human ALCL-derived cells and a murine model of ALK-transformed cells, we show that the AU-binding protein HuR binds to the 3′-UTR of C/EBPβ mRNA, as previously reported in adipocytes, and that NPM-ALK enhances this interaction. Interaction between HuR and C/EBPβ mRNA impacts on C/EBPβ gene expression at both the mRNA and protein levels. Indeed, C/EBPβ mRNA stability following HuR silencing is reduced and reaches the value observed in ALK-inactivated cells. Remarkably, HuR expression is not modified by NPM-ALK, but its association with actively translating polysomes is dramatically increased in ALK+ cells. HuR/polysomes association diminishes when NPM-ALK activity is inhibited and is accompanied by a concomitant decrease of C/EBPβ mRNA translation. Finally, we show that HuR and NPM-ALK colocalized in cytoplasmic granules and HuR is phosphroylated on tyrosine residues in ALK+ ALCL cells. Our study thus demonstrates that C/EBPβ is indeed regulated at the posttranscriptional level by HuR in ALK+ cells, leading us to propose that part of NPM-ALK oncogenic properties relies on its ability to modify HuR properties in the cytoplasm and hence to alter expression of key actors of transformation. Mol Cancer Res; 9(4); 485–96. ©2011 AACR. |
| DOI: |
10.1158/1541-7786.c.6542326.v1 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e9f844ce8d81b2766a9413fc8588579
https://doi.org/10.1158/1541-7786.c.6542326.v1 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....0e9f844ce8d81b2766a9413fc8588579 |
| قاعدة البيانات: |
OpenAIRE |