Question: The protein p53 is important in regulating the cellular response
to DNA damage.
In response to DN…



The protein p53 is important in regulating the cellular response
to DNA damage.
In response to DNA damage, p53 is activated (gene transcript
abundance is
increased, leading to more protein). The p53 protein then inhibits
the cell cycle; it
also initiates apoptosis if the DNA cannot be repaired.
a. What sort of mutation in p53 might be associated with cancer? Be
sure to
address how the mutation would influence the activity of the
protein/gene product.
b. Certain strains of the human papillomavirus (HPV) are associated
with uterine
cancer. The HPV genome codes for several proteins, including E7,
that can bind
to and interfere with the activity of Rb, and E6, that binds to and
interferes with the
activity of p53 (the role for Rb in cancer is illustrated in Figure
23.7 of Pierce).
Would the genes for E6 and E7 be considered oncogenes, or tumor
suppressor
genes? Explain your answer.
Figure 1. The Wnt signal transduction pathway. In the absence
of
Wnt, β-catenin is phosphorylated by casein kinase-1 (CK1) and
GSK-3
in a complex with axin and APC, leading to its ubiquitination
and
degradation. Wnt polypeptides bind to Frizzled and LRP
receptors,
leading to phosphorylation of Dishevelled and LRP. This
provides
binding sites for axin, resulting in dissociation of the
axin/APC/CK1/GSK-3 complex and stabilization of β-catenin.
β-catenin
then translocates to the nucleus and forms a complex with Tcf
transcription factors, converting them from repressors to
activators of
their target genes. Transcription of target genes leads to cell
division
(among other things).
c. Provide an explanation for why it might benefit a virus if its
genome codes for
proteins that interfere specifically with the host proteins p53
and/or Rb (i.e., why
this interference might provide a selective advantage over a
similar virus lacking
this feature).

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