NEOPLASIA 4: p53 gene: The Guardian of the genome. functions, regulation and inactivation

This Short tutorial explains p53 Gene.
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p53 GENE
This is a tumor suppressor gene ( its activity stops the formation of tumors)
Located on 17p13, first discovered in 1979
The p53 protein is the product of p53 gene
P-protein
53- weight of the protein, 53 kDa
Located in almost all normal tissues
Unstable and degrades very quickly
Is one of the most commonly mutated gene in cancer
Function
Regulation of Cell cycle
DNA repair
Apoptosis
Prevents neoplastic transformation either by cell cycle arrest or by triggering apoptosis.
In cases of DNA damage, there is triggering of expression of p53 gene whcich increases the production of p53 proteins. These preoteins Prevent Cell from entering S phase of cell cycle
and Allows time for the DNA repair to take place. also p53 induces DNA repair genes. If the DNA is repaired,the p53 degrades and the cell cycle continues. if the DNA is not repaired, the p53 induces permanent arrest in the cell or activates pro apoptotic proteins bax and bad thereby promoting apoptosis. By these mechanisms, it is understood that the p53 conserves the stability of the cell and thus aptly called as ' THE GAURDIAN OF THE GENOME"
How p53 causes cell cycl arrest?
P53 is the transcriptional regulator of one of the genes named WAF 1
Resulting in increased WAF proteins named as p 21
P21 blocks CDK4/CyclinD complex ….. Cell cycle is halted in G1 stage resulting in cell cycle arrest.
Regulation of p53 protein: by formation of p53 and mdme protein complex which is degraded by ubiquitin mediated pathway.
What happens when p53 is inactivated?
There will be no cell cycle arrest in cases of damaged DNA and the cell cycle progresses with damaged DNa which results in genomic instability and the neoplastic transformation.
How p53 is inactivated??
Mutations
Heterozygous and homozygous loss of alleles
What are the cancers associated with p53 mutations??
Most human cancers!
MC breast, colorectal, liver, lung, and ovarian cancers.
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Please watch: "WARBURG EFFECT: Hallmark of CANCER. What, Why & How?"
• NEOPLASIA 6: WARBURG E...
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I’m a week out from a huge pathology exam and I really wish I’d just studied from your videos from the beginning. I read all this info in a textbook and never retained it, and now it makes so much more sense to me. You break concepts up really well and you also keep it focused on the important stuff. Thank you!

[@MDISLAM-qw7ic]

P53 is guardian of the genome / old man of the genome/ police man of the genome / care taker / gate keeper of the genome . The information which did not get from dr.sparsh gupta & dr.najeeb but i have found amazing & very effective information from your channel. It is why i have subscribed and followed your you tube channel. Thank you sir and i really love " i love pathology " channel..😊

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U are a really wonderful teacher, making the basics so understandable in a simple way, thanks for taking all the efforts in making such wonderful presentations

[@ilovepathologyVijayPatho]

Thank you very much 😊.glad the video was of help 😊 Best wishes.

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Neoplasia was one of the hardest topics i've ever studied and thanks to your videos my concepts are very clear!! please keep uploading more videos on pathology it is indeed very very helpful!!❤❤❤

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Thanks so much..glad these videos are helping 😊 do share with your friends

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I can relate

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Man i really have to thank you so much for your Video. Somehow we dont have anything that easy to understand in germany related to p53 Thanks a lot !!!!!

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Josef Boy Björn same hab nix gefunden

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I love you. This is so well explained i'm in tears.

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Thank you so much sir for making Neoplasia too much easy and understandable😊🎉

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Wow ... Great video. Excellent, detailed yet simplified tuition. Thanks a lot

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Thank you Sir , I am from Pakistan , u made this tough topic much easy to understand , love you

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I have my exam tomorrow n this video helped me to drill the concept really quick... ty ... great explanation...😎🤘

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Best pathology tutorials site I have ever seen.. Really grateful to u .

[@ilovepathologyVijayPatho]

Thank you.

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Thanks to the author，I will finish my paper easily.

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You're a gem sir. Pls upload some more videos. I have my uni exams in 10 days and your videos on neoplasia are a saviour. Keep it up, good luck :)

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Just an amazing clear cut concept I have ever seen🤩

[@chinmayeechhotaray7116]

Thanks dude...i was searching for p53 explanation and ended up in your video with perfect explanation.....you helped me a lot.

[@ChukimeRMarak]

One of the besttttt explanations I've come across. So systematic and made easy to grasp the concept. So grateful to have found this.

[@ilovepathologyVijayPatho]

Thank you 😊

[@lucelence6312]

Thank you so much for making the concept clear and easy to understand

[@OvErShadOweDaZn]

Keep up the good work! I love this video and it was very helpful in understanding. You are a great instructor.

[@cossav2560]

Thank you from London. Great work.

[@20imke]

Thanks for helping me understand it so easily. Textbooks are just overcomplicating everything.

[@svartmetall48]

I realise this is a very brief look at p53, so I'll leave out some of the simplifications, but I would say one thing needs to be corrected regarding the molecular weight. p53 was named because it ran on an SDS-PAGE gel at 53 kDa, not because its molecular weight is 53 kDa. Due to the fact that p53 is quite proline rich it is a more rigid structure with annoying "kinks" in it, and thus it migrates differently on SDS-PAGE. As I am sure you know, proteins don't necessarily migrate at their actual mass (and there are a plethora of reasons for this). p53 is around 44 kDa.

[@svartmetall48]

@johnny torres Probably a good thing if you attend KI. I should know, I taught some of the undergraduate labs that med students took! ;)

[@krishnamanikalita1612]

You are doing great work sir... thank you so much ❤

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Best video ever...pathology would never been so interesting

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Well explained sir. Neoplasia is one chapter that scares me but you have made it more interesting. Your videos have made it more easy for me to go through the text and understand it in a clear way. No amount of paid online classes have made me understand neoplasia as well as these videos . Please keep posting regularly sir!! 🙂

[@priyachakraborty2260]

It was great.... 2moro is my exam nd this video worked for me a lot....

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Thanks sir, really appreciate your hard work and hope to keep loving pathology. Lots of love from Afg🇦🇫

[@ahmedkhan1560]

Excellent presentation. You made this complex topic so simple that I should recommend that it should be used as a template by the Authors of Molecular pathology Books. Thanks a million, Amjad Ali Khan MD USA

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Thank you for the amazing video sir! You explain things so simply!

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Me studying in PG . really u r explained very well and it's very helpfull to understand easily without confusing tq so much sir❤️

[@yashkumarprajapati9648]

Beautifully explained!! Thank you sir 😊

[@elizabethmendes5935]

great explanation and intro to the background of p53!

[@ilovepathologyVijayPatho]

Thank you 😊

[@Artsylove4]

U make all the concepts really easy to understand ... thank you so much sir!!

[@ilovepathologyVijayPatho]

Thanks 😊 Glad you liked them

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Thank you so much for the video because I was very tired with p53

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Thank you so much you made this concept so easy to understand. I was really struggling with this concept. Really helped with studying for my exam!

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You have made us love Pathology ❤️

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Tqs so much for this very easy explanation

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really a good art of teaching...Amazing...

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Thank you so much Sir for such a beautiful explanation. I wish you all the best, may you continue to educate lots of students like me. I study at Imperial College London and will tell my friends about your channel. Thank you!!!

[@ilovepathologyVijayPatho]

Thank you 😊

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Wow so amazing and very clear ty so much ❤

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Thank u so much sir saw this video before going into exam.. got this question today

[@pavansharma8966]

Nicely illustrated about p53 gene regulation in tumor suppression

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Your videos really helps me alot🤝

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Thanku sir a lot i really get concept from ur video thn i can make concept

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Pls do more videos ,its very helpful 🥺

[@CytochromeC]

I m actually dealing a while with p53 but the Video is Great

[@animeloverXinuyasha]

Very good job at outlining this topic - this is a perfect and easy to understand introduction to p53, so now I can go and delve deeper! I do wish you had explained a bit more as to what causes p53 inactivation and how, but all in all great video!

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i love your channel ......all videos are just amazing.......please upload some more videos of pathology #Medico

[@ilovepathologyVijayPatho]

Thanks:-)

[@haroldkumar4766]

Good stuff and explanation! However I wish p53 videos also mention that it's part of the BAX/BAK pathway and Bcl2 as that can be a point of confusion.

[@divyamachevar9156]

You are doing a great job. Please continue doing it, your videos are of great help. Thank you ❤️

[@alienatedaliens]

This was so helpful and clear, thank you!

[@shahidulhchowdhury6411]

wonderful illustration of role of p53 gene

[@munkhbilegenkhbat4492]

very goodjob that explaining p53 also known as guardian of genome. But don't forget some virus can disable cell's p53 protein which means p53 can also protect cell from oncogen viruses like HPV.

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Best teacher

[@j3v167]

Hi. I have read an article where the P53 gene was mentioned. Could you please explain what is meant by mitochondrial translocation of the p53 gene?

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Many thanks for you, you make it very easy

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The concept is clear and easy to understand thanks to the author

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Thank you so much sir❣️

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Great video

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Now I got it completely 🕺

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Yaqeen Yousef Thank you very much 😊

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These are so helpful and easy to understand :) THANK YOU!!!!

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Thank you so much! This was really helpfull and clear.

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Great explanation !

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P53!!!!! Yes!! Thats so cool! I am going to name my child Ilirian P53!

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Thank you sir ..god bless ..you made it so easy to understand 😊

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Thanks for posting this. It was very informative.

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Thank you!!!! The information helped me a lot with my classes

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I'm so glad that it helped

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your lecture is just👌

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Exellent videos regarding neoplasia ,injury etc . But we require more videos regarding other pathological conceptual topics basis Thank you

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Sir this video helps to learn a lot in short🙏🏆

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Great work bro

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Sir, what book do you recommend for exam point of view for second year mbbs?

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the most helpful video! Thank u so much!

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this is a great time saving explanation thanks alot

[@surajmishra1125]

Sir D-CDK4/6 perform Hypophosphorylation or hyperphosphorylation becoz my book mentions E-CDK2 complex for hyperphosphorylating pRb proteins ?

[@satadruray9787]

Hyperphosphorylation of pRB, thereby releasing the transcription factor E2F,.and the latter will then bind to the DNA and initiate the sequence leading to generation of proteins necessary for the cell cycle to progress

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Really helpful. I'm impressed sir. Thank you so much🙂

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Thanku so much sir... Really vey helpful

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Sir kindly make more videos on general path so that our basic concepts will be clear

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Thank you so much for your efforts. Much appreciated!

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Amazing explanation.. Thank you 😊

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Very helpful sir! Thank You :)

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Thankyou ❤

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amazing video! you kept it simple and not too complicated ! :)

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Very nice Crisp and precise

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Good explanation

[@rohit_roars]

Thank you for your explanation sir...

[@HobosRockEmTrashCans]

i learned that the p21 actually stops the CDK2 and cyclin E and therefore stops the cell from entering into the S phase.

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Thank you! The video is very clear!