P53
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E.S.Prakash
Sep 9, 2010, 5:39:17 PM9/9/10
to Medical Physiology at SOM, AIMST University
What is meant by p53 works as a tumor supressor protein. Can you explain more on what would be the effect of a loss-of-function mutation of the p53 gene on cells because I really don't have an idea. Thanks in advance.
Kevin Raj
Year 1 Medical Student
Nicholas Cheong
Sep 9, 2010, 9:47:31 PM9/9/10
to Medical Physiology at SOM, AIMST University
Dear Kevin Raj,
p53 is called a tumor suppressor protein because it activates several
cellular pathways which are known to
halt uncontrolled cellular proliferation. p53 can activate apoptosis
and temporarily arrest cell cycle so that cellular injury can be
"healed". p53 proteins also help initiate DNA repair. Further details
should be available in Robbin's pathology.
Neoplasia is defined as an "abnormal proliferation of cells. The
growth of which exceeds, and is uncoordinated with that of the normal
tissues around it. The growth persists in the same excessive manner
even after cessation of the stimuli". The product of this excessive
cellular growth is known as TUMOR or NEOPLASM. (definition of
neoplasia might have changed slightly, please look up the most up to
date definition)
p53 protein is encoded by TP53 gene. DNA damage or cell cycle
abnormalities are some of the molecular causes of neoplasm. These
factors, fortunately, also activate the TP53 gene, resulting in the
expression of p53 proteins.
So, the expression (production) of p53 proteins depends on the
integrity of the TP53 gene. If the gene is damaged or inactivated due
to any cause like radiation, viral infection and so forth, normal p53
cannot be
produced. Crudely speaking, "loss-of-function mutation" means mutation
(due to any cause) that impairs TP53 gene.
Let me sum up with the help of a flow chart:
Mutated TP53 gene -----> abnormal p53 proteins (dysfunctional) ----->
inability of cells to initiate DNA repair mechanisms or arrest cell
cycle -------> unchecked cellular proliferation -------> cell
overgrowth -------> tumor
Hope this helps.
Humbly,
Nicholas Cheong
MBBS Batch 14
p53 is called a tumor suppressor protein because it activates several
cellular pathways which are known to
halt uncontrolled cellular proliferation. p53 can activate apoptosis
and temporarily arrest cell cycle so that cellular injury can be
"healed". p53 proteins also help initiate DNA repair. Further details
should be available in Robbin's pathology.
Neoplasia is defined as an "abnormal proliferation of cells. The
growth of which exceeds, and is uncoordinated with that of the normal
tissues around it. The growth persists in the same excessive manner
even after cessation of the stimuli". The product of this excessive
cellular growth is known as TUMOR or NEOPLASM. (definition of
neoplasia might have changed slightly, please look up the most up to
date definition)
p53 protein is encoded by TP53 gene. DNA damage or cell cycle
abnormalities are some of the molecular causes of neoplasm. These
factors, fortunately, also activate the TP53 gene, resulting in the
expression of p53 proteins.
So, the expression (production) of p53 proteins depends on the
integrity of the TP53 gene. If the gene is damaged or inactivated due
to any cause like radiation, viral infection and so forth, normal p53
cannot be
produced. Crudely speaking, "loss-of-function mutation" means mutation
(due to any cause) that impairs TP53 gene.
Let me sum up with the help of a flow chart:
Mutated TP53 gene -----> abnormal p53 proteins (dysfunctional) ----->
inability of cells to initiate DNA repair mechanisms or arrest cell
cycle -------> unchecked cellular proliferation -------> cell
overgrowth -------> tumor
Hope this helps.
Humbly,
Nicholas Cheong
MBBS Batch 14
Nicholas Cheong
Sep 10, 2010, 6:03:02 AM9/10/10
to Medical Physiology at SOM, AIMST University
Hi all,
To add on to Nicholas's points (a diagram comparing normal and
abnormal p53 functions is available in Robbins),
the intact p53 is useful in therapy of certain cancers.
As a physiological response, when DNA suffer damage, p53 expression
naturally increases.
Hence cancers with intact p53 when subjected to radiation and
chemotherapy which damages DNA, p53 expression increases and treatment
responses are better. Hence there is a new frontier in treatment of
cancer by increasing p53 activity.
I hope this helps learning come to a full circle.
Best,
Ravi
On Sep 10, 9:47 am, Nicholas Cheong <nicholascheon...@gmail.com>
wrote:
To add on to Nicholas's points (a diagram comparing normal and
abnormal p53 functions is available in Robbins),
the intact p53 is useful in therapy of certain cancers.
As a physiological response, when DNA suffer damage, p53 expression
naturally increases.
Hence cancers with intact p53 when subjected to radiation and
chemotherapy which damages DNA, p53 expression increases and treatment
responses are better. Hence there is a new frontier in treatment of
cancer by increasing p53 activity.
I hope this helps learning come to a full circle.
Best,
Ravi
On Sep 10, 9:47 am, Nicholas Cheong <nicholascheon...@gmail.com>
wrote:
Nicholas Cheong
Sep 10, 2010, 10:39:31 AM9/10/10
to Medical Physiology at SOM, AIMST University
Hi everybody,
Kevin and members of forum: I could not
get a diagram from Robbins (the one Ravi mentioned).
It is very illustrative.
I hope the link I am including below does the trick.
http://p53.free.fr/p53_info/p53_Pathways.html
All best,
Nicholas
On Sep 10, 6:03 pm, Nicholas Cheong <nicholascheon...@gmail.com>
wrote:
Kevin and members of forum: I could not
get a diagram from Robbins (the one Ravi mentioned).
It is very illustrative.
I hope the link I am including below does the trick.
http://p53.free.fr/p53_info/p53_Pathways.html
All best,
Nicholas
On Sep 10, 6:03 pm, Nicholas Cheong <nicholascheon...@gmail.com>
wrote:
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