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Thu, April 7-Lecture 23 end of cell cycle
G0 is controlled by a protein called P53. What if the cell fails to meet conditions, there is too
much damage that it can't be repaired, or it hasn't been replicated properly in the previous cycle,
etc.? We need to be able to prevent that cell (in G0) from ever entering G1. P53 is responsible
for triggering apoptosis (intrinsic apoptosis).
At the same time as it is triggering apoptosis, P53 also triggers numerous microRNAs. Micro
RNAs are genes that are activated and lead to an mRNA (a very short mRNA - hence the 'micro')
is part of a protein complex that is looking for mRNAs that are headed to translation. If the
match is perfect, directly send to degredation. If the match is not perfect, they hold on to them
(still prevents translation from occurring). Why would it be useful to trigger microRNAs, whats
the point? You are sending the cell to apoptosis, don't need to be translating proteins because
you're getting ready to kill the cells off. MicroRNAs are triggered alongside initiating the
apoptotic pathway. How does P53 initiate the apoptotic pathway? P53 is a protein, it is a gene-
regulatory protein able to influence the expression of certain genes. Act not quite like a
transcription factor, but its role is to make sure certain key proteins (Bax, Bak, Apaf1) are
transcribed, translated, active, ready and present to form apoptosomes and get apoptotic cascade
going. The link between regulating the cell cycle and making sure things go smoothly. When you
can't fix it in G0, you have the watchdog that is able to send the cell into apoptosis.
An oncogene is an altered gene that promotes uncontrolled cell division. P53 is NOT an
oncogene. It is a gene regulatory protein, and we call it a tumour suppressor protein because its
intimately involved in the cell cycle and making sure that it controls that the cell will survive or
be sent to apoptosis, we give it this special name because its preventing these tumours from
occurring, its preventing uncontrollable division. When P53 itself is damaged (mutated,
disregulated, etc) it is not longer a tumour suppressor protein or watchdog, it can become an
oncogene (rather than become a solution, it becomes a part of the problem. What happens? P53
can have a mutation (i.e. missense - anything that would change its structure, change how it
interacts with its targets). When a cell is no longer able to pass through G1, you need to signal it
to go to apoptosis, P53 will no longer be able to do its job. It won't be able to promote the cell
going into apoptosis because of the damage that is has, instead its going to allow that cell to keep
going through the cell cycle division. Its going to be able to progress and keep dividing
uncontrollably, ignoring contact inhibition, Hayflick limit etc. it becomes more than
uncontrolled, its over proliferation (can lead to cancer...).
Key difference between somatic cells and germ cells? Gametes. You don't want the cell to be
under stress, so the telomerase is still active (unlike somatic cells). The telomerase will go in,
lengthen it, and fill the gap (don't have that Hayflick limit). When P53 is not doing its job, when
it suffers certain mutations, it has the ability to reactivate the telomerase even in somatic cells.
Now you have a cell that should not be able to complete the cell cycle and continue division
because it has damage. You have P53 thats unable to act as a cellular watchdog and sends those
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