Lecture 12: Biochemistry of Cancer Flashcards
What chromosome can one find the Rb gene?
Chromosome 13
An individual with a deletion of one Rb+ allele is said to be _____.
Predisposed to developing retinoblastoma.
Loss of both Rb+ alleles…
…induces tumor formation.
True or false?
Loss of the Rb gene is found only in retinoblastoma cases.
False.
The Rb gene is frequently missing in several other types of cancer as well.
What are the two forms of retinoblastoma?
- Hereditary.
2. Sporadic.
E2F
A transcription factor that helps transcribe genes whose products are required for the S-phase of the cell cycle.
pRB
The protein product of the Rb gene.
When UN-phosphorylated, it is bound to the transcription factor E2F.
Phosphorylated pRB
Dissociates from E2F, allowing it to exert its effects on the transcription of S-phase-dependent proteins.
Unphosphorylated pRB
Is bound to E2F, keeping it from exerting its effects on the transcription of S-phase-dependent proteins.
Cyclin D and Cyclin E
Bind with cyclin-dependent kinase (CDK) to phosphorylate pRB.
What happens in the absence of pRB?
E2F is left unbound, therefore exerting its effects on the up-regulation of S-phase dependent proteins.
Cells, even with damaged DNA, can continue to replicate.
Many anti-proliferative signals are funneled through which protein?
pRB.
Which protein is the substrate for many “stress-related” phosphorylation events?
p53.
RE
Response element. Usually in reference to the regulatory region where p53 binds.
Once DNA damage is detected (or an oncogene is expressed), what protein is activated?
p53.
What are the two outcomes after p53 has been activated?
- Apoptosis
2. Activation of p21
p21 (two functions)
Activated by p53 when DNA damage is detected.
- Inhibits cyclin/CDK complexes, which in turn halt the cell cycle.
- Binds to PCNA (clamp), inhibiting progression of replication forks.
Many cancer cells do not undergo apoptosis due to what is thought to be an absence of what protein?
p53.
What type of cancer(s) does the following tumor suppressor, when dysfunctional, cause?
RB
Retinoblastoma