Posts Tagged ‘p53 antibody’

S100A6: Playing Roles in Cancer, Apoptosis & Transcription Regulation

Thursday, January 26th, 2012

S100A6 antibodies detect a small calcium binding protein with 2 EF-hand structures and belongs to the S100 family. Calcium binding induces a conformational change of the protein which in turn permits its interaction with several target proteins. It is predominantly expressed in fibroblasts and epithelial cells and has been implicated in several cellular processes such as cell cycle progression, cytoskeleton rearrangement and exocytosis. It is a predominantly cytoplasmic protein however in the presence of calcium ions it might also associate with cell membranes.  Its vast array of biological processes may be due to the fact that it has the ability to bind a number of proteins and modulate their function by inducing conformation changes and/or interfering with post-translational modifications.

The upregulation of S100A6 has been reported in a number of tumors and linked to metastasis.  Recent studies have demonstrated a strong link between high nuclear expression of S100A6 and poor survival in pancreatic cancer patients.  It was concluded that up-regulation of S100A6 is an early event in pancreatic cancer development and that elevated levels of nuclear S100A6 influence the clinical outcome.

S100A6 has also been linked to apoptosis.  It has been shown to enhance the cell death rate of cells under apoptotic conditions when upregulated.  This is believed to be due to the interaction between S100A6 and Caspase 3 during which S100A6 is thought to modulate the transcriptional regulation of caspase 3 by increasing its promoter activity.

P53 appears to be another protein which S100A6 interacts with.  The presence of S100A6 results in higher p53 transcriptional activity which resulted in a higher cell susceptibility to apoptosis induced by hydrogen peroxide.  The binding of S100A6 to p53 did not however affect the ability of p53 to bind to DNA.

As S100A6 is further studies, more protein binding partners are bound to be discovered.  This may shed more light on the diverse roles that S100A6 plays in a vast array of cellular processes. Novus offers top quality S100A6 antibodies as well as lysates, recombinant proteins, RNAi and many other support reagents. Please contact our technical support department (technical@novusbio.com) for any additional details.

Recent developments in p53 antibody research

Friday, January 6th, 2012

P53 is a stress-activated transcription factor, encoded by the TP53 gene. An important tumor suppressor, the protein mediates cellular growth and proliferation, regulating proteins involved in the stress-response. In p53 antibody studies, the protein has been shown to play an important role in the cellular response to DNA damage. Activation of p53 in response to stress stimuli may promote either cell cycle arrest followed by DNA repair, or apoptosis. We at Novus Biologicals are major antibody suppliers of p53 research products.

TP53 is one of the most widely mutated oncogenes, being linked to a large number of carcinomas. It is estimated around 50% of all tumors feature genetically modified or inactivated p53. Not surprisingly, the p53 antibody is widely used in cancer research. Although the function of the protein is to arrest the cell cycle in response to cellular stress, studies have shown that in its mutated form P53 may act as both a tumour suppressor and promoter.

Numerous studies have shown the p53 transcription factor plays transcriptional, posttranscriptional, and posttranslational roles, targeting multiple genes and microRNAs connected to a wide range of cellular activities apart from apoptosis and regulation of cell cycle arrest. In vivo and in vitro studies have shown p53 to be phosphorylated at multiple sites, by a number of different protein kinases, leading to an extensive database of p53 antibody products. Novus is able to supply conjugated and non-conjugated p53 antibody reagents targeting both the entire protein and specific epitopes, suitable for use in a wide range of normal and cancer cell lines.

Mutant p53 Disrupts ASK-1 Induced MAPK Pathways

Wednesday, March 10th, 2010

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.

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.