p53 Tumour Suppressor and MDM2

Regulation and action of p53
To learn about cyclins and CDKs: • Cyclins and CDKs Cell ...

[@jazminazucenadelgadoortega7154]

Awesome! It truly helped me understand the regulation of the cell cycle (in addition to your other video about cyclins). I'd been reading about it but didn't truly get anything... until I found your video, thanks!!! loved it

[@NeuralAcademy]

So glad to have helped ^_^

[@LittleSuzi101]

Found this exactly a year later and it is still as useful! Thank you! :)

[@reddot8605]

p53 does not function according to the 2 hit theory. Since it's active form is a tetramere, a mutation to 1 allele of the p53 gene would make it so that 15/16 active p53 complexes are disfunctional and only 1/16 is effective. 1 mutation is enought to create a significant loss of function

[@Abdulredhamuhanna]

You just saved me! Very comprehensive and concise. Can I just ask, if you don’t mind, what sources you have read, related to this video? Thanks !

[@NeuralAcademy]

I'm so glad to have been helpful!!! :-D Unfortunately, since this video was made months ago, I no longer remember what sources I used... generally I look at either textbooks or research papers.

[@lashahnramikie4226]

Absolute life saver!

[@charlesharris522]

brilliant

[@lowkeyrings9221]

2:25 you failed to explain some of the most important concepts as you were jumping around from activation and deactivation of cell cycle arrest. Cyclin D, cdk4/6 phosphorylate pRb which deactivates pRb(a tumor suppressor gene). If you deactivate an antagonist you are essentially proceeding the cycle. So in summary, cyclin D’s help deactivate a tumor suppressor known as pRB, this normally occurs when there is no cell damage and therefor G1 proceeds to S phase.

[@emmacavalier]

That was explained in the previous video.

[@scienceofcambridge]

Hi, nice video! I hope this is not a dumb question. I think I get the gist of p53 ie. It's a type of QA inspector for DNA and if dna Damage exists it triggers cell death or senecense. What I don't understand is how and what 'damage' is detected? *What* gets spotted as 'not right'? Eg. if you were a QA inspector for say chairs you might count the number of legs, check the lengths of the legs were equal, check the thickness of the legs etc to determine whether or not to reject the chair. Kind Regards, Simon.

[@HPo10tial]

Hi Simon, that's a very good question. In response to DNA damage, (e.g. single or double strand brakes) different sensors such as ATM kinase are activated, which phosphorylates p53 at specific positions. This leads to stabilization of and accumulation of p53. Once p53 accumulates inside the cell's nucleus, it induces transcriptional of either cell cycle inhibitors (e.g. p21) or proapoptotic genes (e.g. PUMA, Bax) depending on the extent of DNA damage (i.e. number of single- or double-strand brakes). This is a good reference if you want more info: www.nature.com/articles/nrm3546/figures/3

[@Messssyybun]

Great job ❤

[@wisemanmkhize6579]

Great one!

[@sumayyah_ibm]

Thank you ❤️

[@CHEH_tf]

Can you make a video specifically on the RCP? Replication Control Point, or just the control points in general: DDCP, RCP and MCP

[@margaritadamai5450]

it was really easy and perfect!!!

[@texemplarstudios5481]

1:24 THAT PURPLE CELL'S FACE 😂😂

[@Abdullah1Hosseini]

Awesome content! Great use of visual cues, microphone could use an upgrade!

[@NeuralAcademy]

Glad you like my content! Could you please clarify the comment about my microphone? I bought a pretty nice one early last year and spend a long time audio editing the script for each video. Do you think the audio should be louder?

[@Abdullah1Hosseini]

@@NeuralAcademy What microphone are you using? What editing software? How much db is the output audio in the video editor and do you equalize it? I try to compare this video to one of CGP Grey's and maybe I have to admit that it might be the tonality of voice? You seem to have a bit of a nasal speech (NOT judging and definitely very grateful for your content) but it is something I personally came across as a bit more monotone and less memorable. Tonality and intention give a lot of cues to how events happen and especially in subjects like physiology it can make the difference. Your visuals are very nice and interesting, but if I look at this vs one of kurzgesagts video's (I know they have a humongous production behind them and you do it maybe alone) it feels a bit bland. Again I recommended your video's and I think they are great, I also always try to give constructive feedback with the intention to make things better. Let me know what you think, a few vocal sessions could hugely improve your way of speaking/teaching. Greetings from Amsterdam.

[@NeuralAcademy]

​@@Abdullah1Hosseini Thank you so much for taking the time to give me this very kind and helpful feedback! I've had comments about the tonality of my voice before but they have been a lot less constructive and polite. I use the Audio-Technica AT3035 Cardioid Condenser Microphone and edit in Adobe Audition. Not sure what you mean by db in the output audio, but I save it as 48000 Hz, 32 bit and make sure the audio is in the yellow zone of volume in Audition. I've only recently started equalizing the audio (you’re right - I’m a one person crew, still learning how to make these videos, and continuously trying to improve them). I have started having my husband record the audio to my videos because I think he has better tonality of voice than me. If you get a chance, I would really appreciate your thoughts. Here is a video he recorded: kzbin.info/www/bejne/eWPKipuKbqelo7M Greetings from Canada!! :-D

[@Abdullah1Hosseini]

@@NeuralAcademy I aced my exam today partly because of you and think very highly of you for taking the time and effort to make this, you are awesome and can only get more awesome! Add me on Instagram if you ever want some vocal or acting tips. 🔥🔥 @seyed.jpg

[@NeuralAcademy]

OHHH!!! Didn't realize this before but I didn't quite understand how to equalize audio properly! This is quite the breakthrough! THANK YOU!!! :-D

[@heythered3208]

That helped a lot! Best wishes from Germany 👍🏻

[@Bromocriptine777]

Very nice

[@maddy4523]

Haha echt so, ein kleiner Hoffnungsschimmer für meinen Test morgen🤡

[@gjjakobsen]

Thanks for making an easy to understand and entertaining video. I'm curious why, when certain nutlins are used to inhibit MDM2, patients with myeloproliferative neoplasms see a transient rise in P53 mutations. A rise in P53 mutations appears to correlate with progression to higher risk accelerated/blast phase and AML, meaning that while MDM2 antagonists may offer apoptotic benefit, they may concurrently accelerate accumulated mutations as well.

[@zdesnichegonetu]

how did I end up here

[@90klh]

Soooo when p53 permanently arrests a cell but does NOT induce apoptosis does that mean the cell is senescent? Just sort of hanging around and getting in the way but otherwise causing no harm?

[@Rbdextrorr]

Love from India🇮🇳🎉❤❤❤❤❤❤

[@skyebenyon2374]

P53 is a dominant negative allele…one allele corrupted is enough to inactivate p53

[@caseyandtoryshalloween1236]

The video is cute and reminds me of dumb ways to die

[@Rick_Sanchez_Jr.]

What about BRCA1, BRCA2 and PARP?

[@chx99]

Nice explanation!!! Thank you so much ♥

[@sincerelydrewcesar]

Do you do the voiceovers for Sketchy?

[@kamweru86]

Awesomely done.

[@mibrh3751]

Presentation is awesome

[@ashwinipatil2106]

PLEASE make video on glycolysis, TCA cycle ond oxidative phosphorylation

[@indiabiologyexplains5013]

I have a question. I know that in order for cell arrest to occur, p53 and mdm2 have to be phosphorylated in order to inhibit their interaction. But what kinase facilitates this reaction?

[@teeliarif2306]

Does p53 inhibits the activation of those genes responsible for apoptosis or overexpress them??? confusion.

[@konanko169]

will you make a video about oncogenic viruses ???

[@manjildiganta9556]

Could you explain BRCA 1 and what happens when it is mutated

[@ALASKAOO7]

video molto utile. Grazie!

[@alejandramiranda8469]

I love the creativity of your videos.

[@ximem3007]

This is amazing. Thank you so much

[@paulntalima6998]

Awesome this is what i needed to know

[@mohammadgalehdari525]

That was really informative! Thanks a lot from Iran.

[@ujjainimukherjee4328]

Amazing animation! It helps a lot

[@anleyteferra7846]

Thank you!

[@mariociencia12]

Excellent!

[@innate-videos]

This is a great video, very clear and with lots of content

[@konanko169]

explain apoptosis

[@Beanssss_]

It's a fancy word for "cell death" usually caused by cell damage. The cells literally tell themselves to "kill themselves" because of something called cell signaling to prevent cancer or mutations. Much like how you get sunburns because you stood in the sun for too long, your cells are literally killing themselves to save you This may be 6 months late but I hope this helps