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Discussion Starter · #1 ·
An 18-year-old lifeguard sits in the sun all day wearing only a swimsuit, a t-shirt, and sunglasses. As UV-B rays damage the DNA of the squamous cells on the lifeguard's ear, which of the following steps is the first to occur?
  • BAX gene transcription is activated
  • Cyclin/CDK complex is inhibited
  • GADD45 transcription is stimulated
  • p21 transcription is stimulated
  • p53 degradation is halted and the enzyme is modified
 

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E. p53 degradation is halted and the enzyme is modified?

We are speaking of squamous cell carcinoma i think here.

BAX gene transcription is activated - I don't think they undergo apoptosis which would be the result of BAX genes.
Cyclin/CDK complex is inhibited - this may eventually happen but p53 degradation is halted and enzyme is modified first (which is what the question is asking).
GADD45 transcription is stimulated - i have no idea what is this.
p21 transcription is stimulated - i have no idea what is this.
 

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Discussion Starter · #7 ·
E is correct!

The correct answer is E. p53 degradation is halted and the enzyme is modified.

In response to DNA damage or other types of stress, the N-terminal end of p53 is phosphorylated, disrupting the binding of Mdm2, an inhibitor of p53 and an ubiquitin ligase. With less Mdm2 binding, more p53 remains in the nucleus and its half-life increases. The C-terminal end is also acetylated by transcriptional coactivators, further promoting p53's regulatory activity. p53 stimulates the transcription of the genes producing GADD45 (C) and p21 (D). p21 block's cyclin/CDK's (B) phosphorylation of Rb, so E2F remains inhibited and progression through the cell cycle is halted. If the damage is repaired, Mdm2 (whose transcription is also stimulated by p53) will eventually regain control over p53 levels. If the damage is not repaired, p53 will promote both transcription and activation of Bax, the pro-apoptotic Bcl-2 protein (A).

I couldn't find just the right illustration - anyone have a good one? Here's a simple one from wikipedia:

P53_pathways.jpg
click image to enlarge
 
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