Academic Journal
Genetic inactivation of Par4 results in hyperactivation of NF‐κB and impairment of JNK and p38
| العنوان: | Genetic inactivation of Par4 results in hyperactivation of NF‐κB and impairment of JNK and p38 |
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| المؤلفون: | Garcia‐Cao, Isabel, Lafuente, María José, Criado, Luis M, Diaz‐Meco, María Teresa, Serrano, Manuel, Moscat, Jorge |
| المصدر: | EMBO reports ; volume 4, issue 3, page 307-312 ; ISSN 1469-221X 1469-3178 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2003 |
| الوصف: | The Par4 gene was first identified in prostate cells undergoing apoptosis after androgen withdrawal. PAR4 was subsequently shown to interact with, and inhibit, atypical protein kinase C isoforms, functioning as a negative regulator of the NF‐κB pathway. This may explain its pro‐apoptotic function in overexpression experiments. To determine the physiological role of PAR4, we have derived primary embryonic fibroblasts (EFs) from Par4 −/− mice. We show here that loss of PAR4 leads to a reduction in the ability of tumour necrosis factor‐α (TNF‐α) to induce apoptosis by increased activation of NF‐κB. Consistent with recent reports demonstrating the antagonistic actions of NF‐κB and c‐Jun amino‐terminal kinase (JNK) signalling, we have found that Par4 −/− cells show a reduced activation of the sustained phase of JNK and p38 stimulation by TNF‐α and interleukin 1. Higher levels of an anti‐apoptotic JNK‐inhibitor protein, X‐chromosome‐linked inhibitor of apoptosis, in Par4 −/− EFs might explain the inhibition of JNK activation in these cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/sj.embor.embor769 |
| الاتاحة: | http://dx.doi.org/10.1038/sj.embor.embor769 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.embor.embor769 https://onlinelibrary.wiley.com/doi/pdf/10.1038/sj.embor.embor769 https://onlinelibrary.wiley.com/doi/full-xml/10.1038/sj.embor.embor769 https://www.embopress.org/doi/pdf/10.1038/sj.embor.embor769 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.3F43F873 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/sj.embor.embor769 |
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