Flashcards in Oncogenes, TSGs and unrestrained growth -L3 Deck (47)
What effects upon proliferation do nuclear receptors induce ?
they can be either pro or anti-proliferative and their roles can change in a cell dependent complex
What do nuclear receptors do and what regulates them ?
they interact and modulate other growth signals
regulated by cofactors and by each other
can be unregulated in cancer
What are examples of nuclear receptors ?
Vitamin D receptor VDR
vitamin A receptor RAR
cholesterol/bile acids/oxysterols (LXR)
hormones AR, ER, PR
What do TSGs encode?
they encode proteins that normally restrain cell division and if mutations occur in these genes these restraints are removed
What are mutations in TSGs and what does it mean ?
they are genetically recessive
- this means that you need mutations on both alleles
- if you inherit one correct copy and one defective copy you will not be diseased
What does loss of heterozygosity mean ?
its when you develop a mutation in your good copy causing mutations in both alleles
- loss of the copy that was protecting you
What is p53 gene known as and why ?
known as the "guardian of the genome"
it halts cell division
How many cancers involve p53 mutations and what do they cause ?
half of all known cancers involve mutations in p53
- most other cancers will have mutations upstream or downstream of p53
mutations lead to half life extension
What actually is p53?
it is a transcription factor with more than 100 gene targets
What down regulates p53 at the protein level ?
down regulated at the protein level by Mdm2
What does Mdm2 do to p53?
as soon as Mdm2 binds p53 it degrades it - it regulates stability
in the absence of Mdm2 p53 is unregulated
What do many of the mutations in p53 mean ?
they mean that Mdm2 cant degrade it
What happens when p53 induces p21?
it prevents hyperphosphorylation of Rb which induces G1/S growth arrest- if this becomes irreversible (SENESCENCE)- the cell cant go through the checkpoints
When does senscence occur?
if the cell is maintained in arrest for too long
What can high levels of p53 induce ?
can induce apoptosis (via bax) in response to excessive levels of DNA damage
What happens when p53 is lost ?
it allows replication of damaged DNA, loss of apoptotic responses and lack of senescence