Reactome | MDM2 ubiquitinates TP53

MDM2 ubiquitinates TP53

Stable Identifier

R-HSA-6804879

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 TP53 (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 TP53 (Homo sapiens)

General

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SVG | | PPTX | SBGN

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MDM2 is an ubiquitin ligase whose expression is positively regulated by TP53 (p53) (Wu et al. 1993). MDM2 binds TP53 tetramer (Maki 1999) and promotes its ubiquitination and subsequent degradation (Fuchs et al. 1998). Formation of MDM2 homodimers (Cheng et al. 2011) or heterodimers with MDM4 (MDMX) is needed for efficient ubiquitination of TP53 (Linares et al. 2003). While MDM2-TP53 binding occurs at the amino-terminus of TP53, MDM2 ubiquitinates TP53 lysine residues at the carboxy-terminus. Acetylation of those lysines can inhibit MDM2-dependent ubiquitination (Li et al. 2002).

Literature References

PubMed ID	Title	Journal	Year
12421820	Acetylation of p53 inhibits its ubiquitination by Mdm2 Li, M, Luo, J, Brooks, CL, Gu, W	J. Biol. Chem.	2002
8319905	The p53-mdm-2 autoregulatory feedback loop Wu, X, Bayle, JH, Olson, D, Levine, AJ	Genes Dev.	1993
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
9824166	Mdm2 association with p53 targets its ubiquitination Fuchs, SY, Adler, V, Buschmann, T, Wu, X, Ronai, Z	Oncogene	1998
10722742	Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 Fang, S, Jensen, JP, Ludwig, RL, Vousden, KH, Weissman, AM	J. Biol. Chem.	2000
14507994	HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53 Linares, LK, Hengstermann, A, Ciechanover, A, Muller, S, Scheffner, M	Proc. Natl. Acad. Sci. U.S.A.	2003
10347217	Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2 Maki, CG	J. Biol. Chem.	1999