p53

By Jamshed Arslan Pharm.D.

By Christina Towers, PhD.

By Jamshed Arslan Pharm.D.

A tissue microarray is a fairly recent high-throughput application that allows researchers to test hundreds of tissue samples with antibodies of their choice at once.  Essentially, a tissue microarray is a paraffin block that is produced by a composition of tissue cores from paraffin donor blocks within defined coordinates to account for a variety of tissue types.

Apoptosis, or programmed cell death, is controlled by a caspase signal cascade that activates downstream signals to induce the morphological changes used to differentiate apoptosis from other forms of cell death.  Novus Biologicals offers a variety of antibodies and tools to detect the different morphological indicators of cell death. 

Head and neck squamous cell carcinoma is quite common in the U.S., covering more than 4% of all cancers each year, and is most susceptible to individuals between 50 and 60 years of age.  Squamous cells are a type of epithelial cell that are located all over the body with concentrations in the mouth, throat, neck and cervix.  EGFR, or epidermal growth factor receptor, is a trans-membrane glycoprotein that oversees cellular proliferation through its intrinsic tyrosine kinase activity.  When EGFR is bound to its ligand, it is phosphorylated by inner tyrosine kinase activity, where down

p53, the protein product of the tp53 gene, is one of the most widely studied tumor suppressor proteins in cancer research.  p53 is unique in that it demonstrates both tumor suppressive and tumor progressive properties depending on whether it is functional or mutated.  The most common mutation in the p53 protein that leads to lack of tumor suppression activity is a missense mutation, however frameshift or nonsense mutations are also common.  In fact, mutant p53 has exhibited dominant negative inhibition of the wild type version of the protein, demonstrating the fact that the p53 pat

The c-Jun N-terminal kinase (JNK) family is a group of regulatory kinases with important functions in cell morphogenesis, inflammation, differentiation, and cell death (1). Aberrant activation of JNK family proteins in cancers has led to interest in small molecule JNK inhibitors as a therapeutic strategy (1). JNK1, also known as MAPK8, is expressed in most tissues and is involved in transduction of extracellular signals such as growth factors or cytokines though a phosphorylation cascade to elicit diverse intracellular responses (1).

p53 is a tumor suppressor that has a central role in regulating cell cycle arrest, DNA repair, and apoptosis. p53 is widely studied for its role in cancer and is mutated or altered in more than half of all cancers (1). This widespread role in tumorigenesis has made p53 one of the most highly studied proteins and a target for anti-cancer therapeutics. Normally, p53 allows cells to sense and respond to cellular stress such as DNA damage or hypoxia (2). In response to these signals, p53 is activated through post-translational modification and protein stabilization.

Ataxia telangiectasia mutated (ATM) is essential for the maintenance of genomic stability. ATM is a 370 kDa serine-threonine kinase that is constitutively expressed in various tissues. Although primarily nuclear, ATM is also found at lower levels associated with cytoplasmic vesicles. As a PI 3-kinase family member, ATM is able to phosphorylate a wide variety of substrates including proteins involved in sensing and repairing DNA damage such as p53 and Brca1 (2). Normally ATM is found as an inactive homodimer.