Genetic inactivation of Par4 results in hyperactivation of NF-kappaB and impairment of JNK and p38 |
| |
Authors: | Garcia-Cao Isabel Lafuente María José Criado Luis M Diaz-Meco María Teresa Serrano Manuel Moscat Jorge |
| |
Institution: | Isabel Garcia-Cao, María José Lafuente, Luis M. Criado, María Teresa Diaz-Meco, Manuel Serrano, and Jorge Moscat |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|