Proto-Oncogenes and Oncogenes
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A proto-oncogene is a normal
A proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate the cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon acquiring an activating mutation, a proto-oncogene becomes a tumor-inducing agent, an oncogene.Examples of proto-oncogenes include RAS, WNT, MYC, ERK, and TRK. The MYC gene is implicated in Burkitt's lymphoma, which starts when a chromosomal translocation moves an enhancer sequence within the vicinity of the MYC gene. The MYC gene codes for widely used transcription factors. When the enhancer sequence is wrongly placed, these transcription factors are produced at much higher rates. Another example of an oncogene is the Bcr-Abl gene found on the Philadelphia chromosome, a piece of genetic material seen in Chronic Myelogenous Leukemia caused by the translocation of pieces from chromosomes 9 and 22. Bcr-Abl codes for a tyrosine kinase, which is constitutively active, leading to uncontrolled cell proliferation. (More information about the Philadelphia Chromosome below)An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
Most normal cells will undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered and malfunctioning. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead.[3] Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they will predispose the cell to cancer; thus, they are termed "oncogenes". Usually multiple oncogenes, along with mutated apoptotic or tumor suppressor genes will all act in concert to cause cancer.
The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation:
A mutation within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure, causing
an increase in protein (enzyme) activity
a loss of regulation
An increase in the amount of a certain protein (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
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)
There are 2 different types of chromosomal translocations that can occur:
translocation events which relocate a proto-oncogene to a new chromosomal site that leads to higher expression
translocation events that lead to a fusion between a proto-oncogene and a 2nd gene (this creates a fusion protein with increased cancerous/oncogenic activity)
Most normal cells will undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered and malfunctioning. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead.[3] Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they will predispose the cell to cancer; thus, they are termed "oncogenes". Usually multiple oncogenes, along with mutated apoptotic or tumor suppressor genes will all act in concert to cause cancer.
The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation:
A mutation within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure, causing
an increase in protein (enzyme) activity
a loss of regulation
An increase in the amount of a certain protein (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
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)
There are 2 different types of chromosomal translocations that can occur:
translocation events which relocate a proto-oncogene to a new chromosomal site that leads to higher expression
translocation events that lead to a fusion between a proto-oncogene and a 2nd gene (this creates a fusion protein with increased cancerous/oncogenic activity)
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