Reactome | MDM2 ubiquitinates phosphorylated MDM4

MDM2 ubiquitinates phosphorylated MDM4

Stable Identifier

R-HSA-6804724

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)
        
        MDM2 ubiquitinates phosphorylated MDM4 (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)
        
        MDM2 ubiquitinates phosphorylated MDM4 (Homo sapiens)

General

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Once MDM4 is phosphorylated by ATM and CHEK2 in response to DNA damage, MDM2 ubiquitinates MDM4 and targets it for degradation (Chen et al. 2005, Pereg et al. 2005). The presence of MDM4 stimulates auto-ubiquitination of MDM2 (Linares et al. 2003).

Literature References

PubMed ID	Title	Journal	Year
14507994	HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53 Linares, LK, Scheffner, M, Hengstermann, A, Muller, S, Ciechanover, A	Proc. Natl. Acad. Sci. U.S.A.	2003
16163388	ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage Lane, WS, Chen, L, Pan, Y, Chen, J, Gilkes, DM	EMBO J	2005
15788536	Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage Shiloh, Y, Meulmeester, E, Jochemsen, AG, Pereg, Y, Teunisse, AF, Shkedy, D, de Graaf, P, Biton, S, Lehmann, WD, Edelson-Averbukh, M, Salek, M	Proc Natl Acad Sci U S A	2005