| Autor: |
Garcia-Cao I; Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autonoma de Madrid, Canto Blanco, 28049 Madrid, Spain., Lafuente MJ, Criado LM, Diaz-Meco MT, Serrano M, Moscat J |
| Jazyk: |
angličtina |
| Zdroj: |
EMBO reports [EMBO Rep] 2003 Mar; Vol. 4 (3), pp. 307-12. |
| DOI: |
10.1038/sj.embor.embor769 |
| Abstrakt: |
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-kappaB 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-alpha (TNF-alpha) to induce apoptosis by increased activation of NF-kappaB. Consistent with recent reports demonstrating the antagonistic actions of NF-kappaB 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-alpha 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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