Proto-oncogene: A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer. Proto-oncogenes may have many different functions in the cell. Some proto-oncogenes provide signals that lead to cell division. Other proto-oncogenes regulate programmed cell death (apoptosis).
The defective versions of proto-oncogenes, known as oncogenes, can cause a cell to divide in an unregulated manner. This growth can occur in the absence of normal growth signals such as those provided by growth factors. A key feature of oncogene activity is that a single altered copy leads to unregulated growth.
Many cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target those DNA sequences and their products
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.
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
o an increase in protein (enzyme) activity
o a loss of regulation
* An increase in protein concentration, caused by
o an increase of protein expression (through misregulation)
o an increase of protein stability, prolonging its existence and thus its activity in the cell
o 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
o an increased gene expression in the wrong cell type or at wrong times
o 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.
There are two mechanisms by which proto-oncogenes can be converted to cellular oncogenes:
Quantitative: Tumor formation is induced by an increase in the absolute number of proto-oncogene products or by its production in inappropriate cell types.
Qualitative: Conversion from proto-oncogene to transforming gene (c-onc) with changes in the nucleotide sequence which are responsible for the acquisition of the new properties.[12
types of protooncogenes
RAS: protiens codes for gtpases for cellular signaltransduction
WNT: signalling pathway concentrated in embryogenesis
MYC: codes for protienbs that bind to another dna
ERK: extra cellular signal regulated kinases regulation of meosis and mitosis
TRK: tyrosine kinases concentrated with nervous cell differentiation