Cellular oncogenes

Abbreviations Akt AKT8 virus oncogene cellular homologue... 

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

Normal cellular gene, usually concerned with the regulation of cell proliferation that can be converted to a cancer promoting oncogene by mutation. 

In concordance with the central role of ubiquitin modification in multiple cellular functions perturbations of this system are associated with a variety of diseases. Defects in the control of cell cycle regulators by the ubiquitin proteasome system are connected to cancer progression and many E3 ligases were originally identified as oncogenes. 

Gubits, R.M. Fairhurst, J.L. (1988). c-fos mRNA levels are increased by the cellular stressors, heat shock and sodium arsenite. Oncogene 3, 163-168. 

Fox TR, Watanabe PG. 1985. Detection of a cellular oncogene in spontaneous liver tumors of B6C3F, mice. Science 228 596-597. 

Protein kinase B, or Akt, was discovered as the product of an oncogene of the acutely transforming retrovirus AKT8, causing T-cell lymphomas in mice. It encodes a fusion product of a cellular serine/threonine protein kinase and the viral structural protein Gag. This kinase is similar to both protein kinase Ce (PKCe 73% identity to the catalytic domain) and protein kinase A (PKA 68%). It differs from other protein kinases in that it contains a pleckstrin homology (PH) domain, which allows it to bind to polyphosphoinositide head groups (and also to G-protein fly subunits). To date, three subtypes have been identified a, (3, and y, all of which show a broad tissue distribution. It... 

Components of Tyrosine Kinase Signal Transduction Cascades Are Discovered as Cellular (or Viral) Oncogenes... 

Amundson SA et al. Fluorescent cDNA microarray hybridisation reveals complexity and heterogeneity of cellular geno-toxic stress responses. Oncogene 1999 18 3666-3672. 

Kaushansky, K. and Drachman, J. 2002. The molecular and cellular biology of thrombopoietin the primary regulator of platelet production. Oncogene 21(21), 3359-3367. 

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