The DNA Damage Response | Repair the DNA or Commit Apoptosis?

[@alebazi2011]

CORRECTION NEEDED - hypophosphorylated pRb inhibits E2F. In the case the cell cycle is to be progressing, E2F needs to be released from the complex w/pRB. It means that pRB needs to be phosphorylated!

[@stevenshivers6082]

Correction to your video: Succintly, phosphorylated retina blastoma renders dissociation from E2F. Subsequently, E2F can translocate to the nucleus to confer increased expression of E2F target genes, including E2F (positive feedback loop) and cyclin E to propogate entry into S-phase. CDK = Cyclin-Dependent-Kinase. Per definition, kinases phosphorylate (add phosphor groups to) targets. Thus, CDK will phosphorylate retina blastoma to confer its dissociation from E2F.

[@kalyanRanjit-u4z]

Yes the CDK2/Cyclin E phosphorylates PrB, which can release the factors that allow G1 to S.

[@Diogenesthedog0]

There are already many comments highlighting the mistake and I'll leave a comment too.. During G1 phase, cdk4/6 phosphorylate many proteins required for the progression of the cell cycle and E2f is one of the key proteins which is required for the progression of the cell cycle. In early G1 phase, it's bound to pRb and is in inactivated form pRb when phosphorylated dissociated from the E2f and E2f can then then go to the nucleus and binds to the target Dna sites which includes Gene required for the progression of Cell cycle(S phase) but also it binds to E2f gene itself so more E2f are produced and the cycle progresses. When there's a DNA damage, P21 inhibits the Cdk4/6 complex so it can not phosphorylate pRb along with many other things and thus pRb remain bound to E2f and cell cycle halts.

[@reezis1619]

doesn't the retinoblastic protein release E2F after phosphorylation?

[@jonathanlehmann2059]

I thought so too. From ‘Signal Transduction, Principles, Pathways, and Processes’, page 141: “Phosphorylation of the pRB family proteins by CDKs during G1 phase causes pRB to dissociate from E2Fs, allowing transcription of target genes that stimulate progression into S phase.”

[@reezis1619]

@@jonathanlehmann2059 Yeah. That is what it says in my textbook as well

[@jonathanlehmann2059]

milk is cheap protein Good to know, thanks. Mine is a 2013 book, so it’s possible that the field has changed since then, maybe.

[@AnchaliJunn]

Very nice explanation 😺

[@sudiptasarma]

nicely explained.

[@alhaeri1]

in my opinion it should be more like high degredation of p53 in the case of low stress and low degredation of p53 in the case of high stress

[@dontmissthelittlethings]

Thanks for the information.

[@killianpapail9324]

Isn't the cdk4/6-cyclinD complex which phosphorylates Rb to release E2F ?

[@fatahiyakashif8199]

pRb is inactivated when phosphorylated and then it releases E2F which enters the nucleus and acts as a transcription factor for proteins that help in G1 to S phase transition.

[@seanclark6438]

Just double checking but is P21 negative my regulated by MDM2

[@DocV87]

it is p53 that is degraded by the action of MDM2

[@seanclark6438]

Fayaz Feroz Thanks couldn’t quite remember, when revising this I looked up all the gene loci, thanks to the wink wink to revise p53 and non of it came up on the exam

[@jamesbourke6211]

king