MDM2
MDM2 is an E3 ubiquitin ligase that keeps p53 at low levels in unstressed cells.
Function
MDM2 binds the transactivation domain of p53, masks its ability to activate transcription, shuttles it out of the nucleus, and ubiquitinates it for proteasomal destruction. The gene’s own transcription is activated by p53, so the pair forms a negative feedback loop: p53 rises, drives MDM2 expression, and MDM2 then cuts p53 back down. DNA damage interrupts the loop - ATM phosphorylates both proteins at the residues that matter, and the stress-sensing protein p14ARF sequesters MDM2 - so p53 accumulates until the damage signal clears.
In cancer
The MDM2 gene is on chromosome 12q and
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