A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon ''activation'', a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene. Examples of proto-oncogenes include RAS, WNT, MYC, ERK, and TRK.
Activation
The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic activation types:
- A mutation within a proto-oncogene can cause a change in the protein structure, causing
- an increase in protein (enzyme) activity
- a loss of regulation
- An increase in protein concentration, caused by
- an increase of protein expression (through misregulation)
- an increase of protein (mRNA) stability, prolonging its existence and thus its activity in the cell
- a gene duplication (one type of chromosome abnormality), resulting in an increased amount of protein in the cell
- A chromosomal translocation (another type of chromosome abnormality), causing
- an increased gene expression in the wrong cell type or at wrong times
- the expression of a constitutively active ''hybrid protein''. This type of aberration in a dividing stem cell in the bone marrow leads to adult leukemia
Mutations in microRNAs can lead to activation of oncogenes. New research indicates that small RNAs 21-25 nucleotides in length called microRNAs (miRNAs) can control expression of these genes by downregulating them.Antisense messenger RNAs could theoretically be used to block the effects of oncogenes.
Further Reading
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