Transcript Cell Cycle, Cancer, and the Biology Student Workbench

Cell Cycle, Cancer, and the
Biology Student Workbench
An intro to what BSW can do
2002
Steve Moore & Kathy Gabric
p53
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p53 is a tumor suppressor gene.
It turns on other genes that inhibit the cell cycle.
If p53 is mutated, the mutant form results in a protein
that cannot perform its function. Its disruption is
associated with approximately 50 to 55 percent of
human cancers
As a result, the cell cycle has no “brakes” to slow it
down, and it proceeds at a reckless speed.
p53
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p53 can tell the cell to commit suicide.
This is called apoptosis or programmed cell death.
If p53 is mutated, the cell looses its ability to have
cancer cells kill themselves.
A mutated p53 can be inherited from one
generation to the next. The mutation may cause
cancer, or may make it more susceptible to tumor
causing viruses attaching and inactivating the
gene.
p53: Keeping Cancer in Check
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The p53 tumor suppressor and its surrounding
molecules are now the focus of thousands of
studies in laboratories around the world.
These studies may one day lead to new treatments
for the most frequent and life-threatening of
cancers.
This is what p53 looks like.
How can a scientist studying p53 find
its amino acid sequence?
BSW is a tool to search databases for
protein and DNA sequences.
Lets Begin!
Go to
Just click on the words above to begin. We suggest you
keep this window open and have BSW open in another.
Biology Student Workbench
Click on
–
Student Interface to the Biology Workbench
(SIB) You may have to do this through several
pages.
Type in username and password and then submit
PS. You will have to register first if you have not
yet done so. Its Free!
Create a New Session
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You have numerous options that are self
explanatory.
BSW will save all of your work sessions for
you.
Today, we will create a new session and call it
cancer.
Choose Protein Tools
The tools available to you and a description of
their use is provided for you.
 First use:
Multiple database search for protein
sequences
 Type in p53 and select the GenBank Primate
sequence.
 Click Ndjinn to activate the tool.
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Hard Part!
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Look for Human p53 (TP53) gene, complete cds.
(Complete DNA Sequence)
Lots of other partial sequences, DNA fragments,
exons and introns, and other animal DNA are given.
Place a check next to it and import the sequence.
The sequence will be saved at the bottom of the
page.
Amino Acid Sequences
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Compare a Protein sequence to a protein
sequence database
Choose GenBank Primate Sequences
Check your imported sequence
Activate the tool by clicking on BLASTP
Find a similar protein
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The higher the score, the more closely
related the proteins will be.
In looking for a mutation, they should be
very similar with only a few changes.
For this activity choose tumor protein p53
(Li-Fraumeni syndrome)...
Check it and import the sequence.
Compare the Sequences
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Align multiple protein sequences with each
other.
Select the 2 proteins you have saved.
Activate the tool by clicking on CLUSTALW
Compare the Sequences
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The letters in blue mean that the amino acids are
highly conserved. In real people terms, it means
they are the same.
Notice the change from proline in the normal p53
gene to alanine in the Li Fraumeni p53 gene.
This means that the DNA was mutated and as a
result it coded for the wrong amino acid.
Import this alignment to save it.
So what’s the big problem with 1
wrong amino acid?
Really how different
are proline and
alanine anyway?
Proline vs. Alanine
Proline
I still don’t see what the big
problem is!
What does this little
switch actually do to
the person?
Li Fraumeni Syndrome
Li-Fraumeni syndrome is a cancer prone disease.
Prognosis: most common cancer in Li-Fraumeni
children are : soft tissues sarcoma before the age
of 5 yrs and osteosarcoma afterwards, and breast
cancer in young adults; other frequent cancers:
brain tumors, leukemias, adrenocortical
carcinoma; 1/3 of patients have developed more
than one primary cancer, which is quite
characteristic of Li- Fraumeni syndrome. Cancers
in this disease, as in other cancer-prone diseases,
often occur early in life: 50% of patients aged 30
yrs have had a cancer and 90% have had cancer by
age 60 yrs.
So what about the DNA that
resulted in this?
Choose Nucleic Tools
The tools available to you and a description of
their use is provided for you.
 First use:
Multiple database search for nucleic
sequences
 Type in p53 and select the GenBank Primate
sequence.
 Click Ndjinn to activate the tool.

Hard Part!




Look for Human p53 (TP53) gene, complete cds.
(Complete DNA Sequence)
Lots of other partial sequences, DNA fragments,
exons and introns, and other animal dna are given.
Place a check next to it and import the sequence.
The sequence will be saved at the bottom of the
page.
Find a similar, but mutated sequence.
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Do Ndjinn search for Li-Fraumeni Syndrome
An odd quirk is that you must enter it as
li-fraumeni exactly. Choose the GenBank
Primate sequences & click on Ndjinn
Import this nucleic sequence.
Select both sequences and align them by
clicking on ClustalW
Compare the sequences.
What’s Up?
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How does this compare to what we saw in the
protein sequence?
How can we explain the differences?
BSW is a tool to analyze databases for
protein and DNA sequences.
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This tool can be used for research into proteins
and the important jobs they do.
Or to find out why an alteration in the protein
results in a disease state.
The problem may ultimately lie in the DNA, and
BSW can be used to determine its sequences
to.
How could you use Biology
Student Workbench?
Any ideas for projects
you’d like to try?