L21 - Oncogenes and Tumour Supressor Genes Flashcards
Describe ways in which an Oncogene can become activated?
Mutation or deletion of a gene leads to an encoded protein with an altered structure are function.
Duplication of DNA sequence - more protein is made
A DNA regulatory sequence translocated from distant site alters the expression of a downstream gene. It may lead to increased synthesis of an encoded protein.
Translocation may aso cause a fusion with another gene to make a fusion gene. This causes the synthesis of a fusion protein (contains portions encoded by different genes). It is not under normal control.
What do Proto-oncogenes encode for?
They encode components of the growth factor signal transduction pathway
What 4 types of proteins are nornally involved in the transduction of growth signals?
- growth factors
- growth factor receptors
- intracellualr signal transducers
- nuclear transcription factors
Describe the RAS oncogene family as an intracellular signal transducer?
RAS proteins are small GTPases that are normally bound to GDP in a neutral state. Oncogenic activation of RAS is seen in 30% of cancers.
Point mutations ocur in codons 12, 13, and 61
Single mutation is enough to activate oncogene.
When there is a mutation, RAS protein becomes hyperactive ad issues signals on its own, and so cells are continually dividing
Describe the MYC oncogene family as a transcription factor?
consists of 3 members: C-MYC (codes for c-Myc), MYCN (codes for n-Myc), and MYCL (codes for L-Myc).
These oncogenes belong to a family of transcription factors that regulate transcription of 15% of the entire genome
It activates when it comes under the control of foreign transcriptional promoters, which leads to deregulation of the oncogene that drives relentless proliferation
Activated by chromosomal translocation
State what other oncgenes chromosomal translocation is responsible for, and what cancer is associated with it?
The philadelphia chromosome - it is the product of CT generating the BCR-ABL fusion protein.
ABL is a tyrosine kinase molecule, and as result of this translocation, the tyrosine kinase activity of oncogene ABL is constitutive, leading to abnormal proliferation.
What is Retinoblastoma and where is the hereditary mutation located?
It is a rare childhood cancer that develops when immature retinoblasts continue to grow very fast and do not turn into mature retinal cells.
An eye that contains the tumour will reflect light back in a white colour
The hereditary mutation is on chromosome 13 on the retinoblastoma 1 (Rb1) gene.
Describe the RB protein function and activity?
It regulates the activity of the E2 F transcription factor crucial for the expression of genes required for S phase.
When the Rb tumour supressor is active it an inhibit cell proliferation
Rb is active when dephosphorylated and it remains bound to E2F
When it hyperphosphorylates, it becomes inactive
