Step in succession

Nudation 

Migration 

Ecesis 

Aggregation

Competition 

Reaction 

Stabilization

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p53

tumor-suppressor gene 

arrest of cells with damaged DNA

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#Unit 4. Cell Communication and Cell Signaling

p53

extremely unstable protein and generally does not accumulate to high enough levels to stimulate transcription under normal conditions

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#Unit 4. Cell Communication and Cell Signaling

MDM2

catalyzes the ubiquitinylation of p53 & targeting it for proteasomal degradation

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#Unit 4. Cell Communication and Cell Signaling

Rapid degradation of p53 is inhibited by ATM and ATR, after DNA damage

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#Unit 4. Cell Communication and Cell Signaling

Phosphorylation of p53 on a serine residue in the N-terminus by ATM or DNA-PK displaces bound MDM2 from p53, thereby stabilizing it

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#Unit 4. Cell Communication and Cell Signaling

MDM2 levels in the cytoplasm are controlled by

ATR and p14ARF (p19ARF in the mouse), sequesters it in the nucleolus, where it cannot access p53.