This video presents how dominant negative mutations in the p53 gene yield nonfunctional p53 tetramers. A review of p53 structure and domains is also presented.
Great explanation and effective use of sketch models, you definitely know what you’re doing. Thanks for sharing! Just a question: if a mutation on a single allele were to damage the tetramerization domain, what would happen? I’d say that you’d have a reduction in overall production of p53 but the wild type tetramer would still be able to form (and it’d the only homo tetramer to actually assemble) and so in this case we would not be calling about negative dominance effect - the cell would still retain a functional p53 (at least until heterozygosis is kept). Is this correct?
Thank you for this video. Amazing explanation on p53 missense mutations! I was also wondering if a frameshift mutation in the DNA binding domain affects the function of P53 the same way a missense mutation in the DNA binding domain does.
In the tetramers where one copy of p53 is mutated and the other 3 are wild type, is it not the same tetramer, just rotated? I'm asking because it would mean the chances of having a non-functional tetramer would be less than 94%.
Thank you very much for this video. I would like to ask, if the mutated P53 gene ( in one copy of the gene) is inherited from the parent, does this mean that from infant, the offspring will develop cancer straightaway since unlike the knudson’s 2 hit hypothesis which requires both alleles to be mutated before tumourigenesis, p53 only needs one allele to coz problems or will there have to be some kind of trigger before the offspring develops cancer? Hope you can help me? Thanks
It depends on the mutation inherited. Li-Fraumeni syndrome is typically characterized by inheriting a dominate-negative point mutation in p53, which ends up giving rise to cancer in many organs. If a person inherited a deletion in p53, due to the process of LOH (loss of heterozygosity), the other, normal copy is at high risk for deletion.
*p53 knockout mice can be induced to generate cytotoxic T cells specific for normal p53 that, on adoptive transfer into p53 wild-type mice, can eradicate tumors overexpressing p53 without causing autoimmunity in the host.* Can you explain this? I cant get it😔
very easy to understand, thank you!
Just for more information, p53 binds to DNA via a special zinc finger domain.
Great explanation and effective use of sketch models, you definitely know what you’re doing. Thanks for sharing! Just a question: if a mutation on a single allele were to damage the tetramerization domain, what would happen? I’d say that you’d have a reduction in overall production of p53 but the wild type tetramer would still be able to form (and it’d the only homo tetramer to actually assemble) and so in this case we would not be calling about negative dominance effect - the cell would still retain a functional p53 (at least until heterozygosis is kept). Is this correct?
Thank you my friend.
Thank you so so so so much!!! Greetings from México:)
You are welcome!
Thank you!
Very well explained and the diagrams are very helpful. Thanks man you probably just saved my dissertation.
You’re welcome. Good luck on your defense.
@@JoeDeMasiScience , DR5 is a downstream gene of the p53 tumor-suppressor gene?
OMG THIS IS THE BEST VIDEO EXPLAINING THE P53 TETRAMERS!! Learned more from you then my professors 1 hour lecture 🔥
Wow thanks!
Thank you for this video. Amazing explanation on p53 missense mutations! I was also wondering if a frameshift mutation in the DNA binding domain affects the function of P53 the same way a missense mutation in the DNA binding domain does.
Thank you for explaining in detail
Welcome!
thank u sm !!
Thank u so much
No problem
thank youuu
In the tetramers where one copy of p53 is mutated and the other 3 are wild type, is it not the same tetramer, just rotated? I'm asking because it would mean the chances of having a non-functional tetramer would be less than 94%.
Thank you very much for this video. I would like to ask, if the mutated P53 gene ( in one copy of the gene) is inherited from the parent, does this mean that from infant, the offspring will develop cancer straightaway since unlike the knudson’s 2 hit hypothesis which requires both alleles to be mutated before tumourigenesis, p53 only needs one allele to coz problems or will there have to be some kind of trigger before the offspring develops cancer?
Hope you can help me?
Thanks
It depends on the mutation inherited. Li-Fraumeni syndrome is typically characterized by inheriting a dominate-negative point mutation in p53, which ends up giving rise to cancer in many organs. If a person inherited a deletion in p53, due to the process of LOH (loss of heterozygosity), the other, normal copy is at high risk for deletion.
*p53 knockout mice can be induced
to generate cytotoxic T cells specific for normal p53 that,
on adoptive transfer into p53 wild-type mice, can eradicate
tumors overexpressing p53 without causing autoimmunity
in the host.*
Can you explain this? I cant get it😔
Sir plzzz told which books you followed.
The Immune System by Parham.
Has anyone ever considered trying to use CRISPER CAS 9 to turn P53 back on? Obviously easier said than done
Its probably easier to inhibit the bad p53 gene so that the good p53 gene is the only one producing p53 so only good tetrameres will be formed.