p53 vs. Rb

[usmlesuccess]

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My understanding of Rb protein is that in it's activated state(hypophosphorylated) it basically tells the cell to stop and repair any DNA damage before transitioning from G1 to S phase. p53 phosphorylates Rb and inactivates it, thereby telling the cell to move on. So if p53 is mutated, Rb will be hypophosphorylated and therefore active. Wouldn't the cell just not move onto the S phase.

Can someone explain how Rb and p53 interact?????

 

[Phloston]

My understanding of Rb protein is that in it's activated state(hypophosphorylated) it basically tells the cell to stop and repair any DNA damage before transitioning from G1 to S phase. p53 phosphorylates Rb and inactivates it, thereby telling the cell to move on. So if p53 is mutated, Rb will be hypophosphorylated and therefore active. Wouldn't the cell just not move onto the S phase.

Can someone explain how Rb and p53 interact?????

Rb is phosphorylated by CyclinD-CDK4/6, which enables Rb's dissociation from E2F, thereby enabling E2F-induced transcription and progression of the cell cycle.

Rb is not phosphorylated by p53 (as far as I'm aware).

p53 (protein) is produced from the TP53 gene. p53 binds to DNA and induces transcription of several cell cycle regulatory proteins, including p21. So for p53, I would literally just remember: TP53 gene; induces transcription of inhibitory regulators, including p21; Li-Fraumeni syndrome; tumour-suppressor.

Given that there are thousands (literally) of intra- and inter-cellular proteins regulating the cell cycle, Rb and p53 likely do influence one another via up-/down-stream substrate interactions, but I'm fairly sure the p53-Rb proteins don't directly interact on a level that we need to know for the USMLE.

In mantle cell lymphoma, upregulated CyclinD means increased phosphorylation of Rb.

 

[usmlesuccess]

Thanks phloston. I think in the goljan lectures he made it seem as if they directly influence each other. I think it was in the neoplasm lectures.

 

[Phloston]

Thanks phloston. I think in the goljan lectures he made it seem as if they directly influence each other. I think it was in the neoplasm lectures.

I have to give HY Cell & Molecular Bio a more generous pass closer to my exam date, but I don't recall having read about Rb-p53 direct interaction. I wish I had the book on me, but it's at my other house at the moment, and I had drawn up a diagram about how Ras fit in there too, which I wish I could remember more clearly.

I think it's because constitutive (mutated) Ras upregulates CyclinD (colon cancer, NF1, mantle cell), which in turn leads to transcription through Rb, and p21, which is produced via p53 protein-induced transcription, normally helps to downregulate Ras.

It's annoying because I knew this really well about 6 months ago. At least it's food for thought..