Reactome | ATM phosphorylates MDM2

ATM phosphorylates MDM2

Stable Identifier

R-HSA-6804955

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle Checkpoints (Homo sapiens)
  - G1/S DNA Damage Checkpoints (Homo sapiens)
    - p53-Dependent G1/S DNA damage checkpoint (Homo sapiens)
      - p53-Dependent G1 DNA Damage Response (Homo sapiens)
        
        Stabilization of p53 (Homo sapiens)
        
        ATM phosphorylates MDM2 (Homo sapiens)

Gene expression (Transcription) (Homo sapiens)

- RNA Polymerase II Transcription (Homo sapiens)
  - Generic Transcription Pathway (Homo sapiens)
    - Transcriptional Regulation by TP53 (Homo sapiens)
      - Regulation of TP53 Activity (Homo sapiens)
        
        Regulation of TP53 Expression and Degradation (Homo sapiens)
        
        Regulation of TP53 Degradation (Homo sapiens)
        
        ATM phosphorylates MDM2 (Homo sapiens)

General

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ATM phosphorylates MDM2 on three serine residues (S386, S395, S407) and one threonine residue (T419) in vicinity to the RING domain. ATM-mediated phosphorylation of MDM2 in response to DNA damage (DNA double strand breaks) prevents MDM2 dimerization, binding of TP53 (p53) and MDM2-mediated ubiquitination of TP53 (Cheng et al. 2009, Cheng et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
21986495	Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage Cheng, Q, Cross, B, Li, B, Chen, L, Li, Z, Chen, J	Mol. Cell. Biol.	2011
19816404	ATM activates p53 by regulating MDM2 oligomerization and E3 processivity Cheng, Q, Chen, L, Li, Z, Lane, WS, Chen, J	EMBO J.	2009