Mutant p53 Disrupts ASK-1 Induced MAPK Pathways

Wed, 03/10/2010 - 10:46

MAPK (mitogen-activated protein kinase) antibodies are widely used in cellular research to study these processes, in both healthy and cancerous cells. For example, p38 is a pro-apoptotic factor, and c-Jun NH2-terminal kinase (JNK) regulates cellular longevity and stress resistance. Together they form the JNK/p38 signaling pathway, which is controlled by at least five MAPK cascades.

ASK1, also known as MAPKKK5 and MEKK5, is an apoptosis-regulating kinase which phosphorylates and stabilizes the Daxx protein. The two regulate each other via a positive feedback loop, i.e. higher Daxx levels lead to greater production of ASK1. ASK1 regulates cellular stress, for example that following activation of tumor necrosis factor alpha (TNFα). It is necessary for the sustained activation of JNK.

It has been shown that cancer treatment with TNFα leads to ASK1 activation and accumulation of Daxx. The p53 transcription factor is associated with this pathway, but is easily mutated, and in its mutant form can bind to Daxx. This inhibits the activation of ASK1 and therefore blocks the ASK1 phosphorylation of Daxx. In studies using mutant p53 and Daxx antibody in cancer cells, it was shown that when TM p53 was depleted, the level of Daxx increased and the apoptotic effect of TNFα was restored.

Western Blot: p53 Antibody Western Blot: p53 Antibody

This shows that amplification of the JNK/p38 signaling pathway is important in regulating the cellular response to drug-induced apoptosis. Furthermore, the disruption of this pathway by Tumorigenic mutant p53 can lead to cell stress and tumor development.

The MAPK immunoglobulins that we at Novus Biologicals have in our antibody catalog cover a large number of signaling pathways.

Novus Biologicals offers many p53 reagents for your research needs including:


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