Reactome | Proteasome-dependent degradation of ubiquitinated CDH1

Proteasome-dependent degradation of ubiquitinated CDH1

Stable Identifier

R-HSA-9766223

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

cytosol, early endosome membrane

ReviewStatus

3/5

Locations in the PathwayBrowser

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Cell-Cell communication (Homo sapiens)

- Cell junction organization (Homo sapiens)
  - Cell-cell junction organization (Homo sapiens)
    - Adherens junctions interactions (Homo sapiens)
      - Regulation of Homotypic Cell-Cell Adhesion (Homo sapiens)
        
        Regulation of Expression and Function of Type I Classical Cadherins (Homo sapiens)
        
        Regulation of CDH1 Expression and Function (Homo sapiens)
        
        Regulation of CDH1 Function (Homo sapiens)
        
        Degradation of CDH1 (Homo sapiens)
        
        Proteasome-dependent degradation of ubiquitinated CDH1 (Homo sapiens)

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Proteasome-dependent degradation of ubiquitinated CDH1

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MDM2 acts as an E3 ubiquitin ligase for CDH1 (E-cadherin), promoting its ubiquitin-dependent, proteasome-mediated degradation (Yang et al. 2006, Adhikary et al. 2014). Protein levels of CDH1 (E-cadherin) are decreased in a dose-dependent manner with increasing MDM2 level, which is dependent on the E3 ubiquitin ligase activity of MDM2 and proteasome activity (Yang et al. 2006). In primary tumors of breast cancer patients with lymph node metastasis, protein levels of MDM2 and CDH1 are inversely correlated (Yang et al. 2006). Overexpression of ectopic MDM2 in human breast cancer cell lines enhances cell dissociation, motility, and invasiveness, which is dependent on downregulation of CDH1 and independent of TP53, a well-established MDM2 substrate (Yang et al. 2006). MDM2 was shown to shorten the half-life of CDH1 by pulse chase experiments, and was also shown to reduce the amount of CDH1 at the plasma membrane (Yang et al. 2006).

Literature References

PubMed ID	Title	Journal	Year
25086032	Inhibition of epithelial to mesenchymal transition by E-cadherin up-regulation via repression of slug transcription and inhibition of E-cadherin degradation: dual role of scaffold/matrix attachment region-binding protein 1 (SMAR1) in breast cancer cells Adhikary, A, Chakraborty, S, Mazumdar, M, Ghosh, S, Mukherjee, S, Manna, A, Mohanty, S, Nakka, KK, Joshi, S, De, A, Chattopadhyay, S, Sa, G, Das, T	J Biol Chem	2014
16980628	MDM2 promotes cell motility and invasiveness by regulating E-cadherin degradation Yang, JY, Zong, CS, Xia, W, Wei, Y, Ali-Seyed, M, Li, Z, Broglio, K, Berry, DA, Hung, MC	Mol Cell Biol	2006