Ubiquitinated CDH1 translocates to lysosomes for degradation

Stable Identifier
R-HSA-9935552
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
early endosome membrane, lysosomal membrane
ReviewStatus
5/5
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Ubiquitinated CDH1 translocates to lysosomes for degradation
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ARF6, RAB5, and RAB7 were reported to be involved in trafficking of a recombinant mouse CDH1 (E-cadherin) to lysosome for degradation in MDCK cells upon SRC-facilitated tyrosine phosphorylation and ubiquitination of CDH1 (Palacios et al. 2005). In the human breast cancer cell line MCF7, CBLL1 (Hakai)-mediated CDH1 ubiquitination and internalization leads to lysosome-dependent degradation of CDH1, while the proteasome does not appear to play a significant role (Shen et al. 2008). In the human hepatocellular carcinoma cell line HepG2, CBLL1-facilitated CDH1 ubiquitination and internalization was reported to lead to CDH1 degradation through both proteasomal and lysosomal routes (Chen et al. 2009). The integrin-interacting protein BSG (also known as besigin or CD147) was reported to promote lysosomal localization and degradation of CDH1 in HepG2 cells (Lu et al. 2018). In a study in which recombinant mouse CDH1 constructs, either full-length or just involving the juxtamembrane domain (JMD) of CDH1, were expressed in the canine MDCK cell line, it was found that proteasome is at least partially responsible for degradation of the ubiquitinated CDH1 (Hartsock and Nelson 2012). In the human colon carcinoma cell line T84, IFNG (interferon-gamma)-stimulated internalization of CDH1 is dependent on FYN kinase and CBLL1, and both lysosome and proteasome contribute to degradation of internalized CDH1 (Smyth et al. 2012). RAF kinase may promote the sorting of internalized CDH1 from the endosome to the lysosome compartment rather than to the recycling route (Janda et al. 2006).
Literature References
PubMed ID Title Journal Year
29356040 Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress

Lu, M, Wu, J, Hao, ZW, Shang, YK, Xu, J, Nan, G, Li, X, Chen, ZN, Bian, H

Hepatology 2018
18057010 Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal growth factor receptor to Src-mediated pathway

Shen, Y, Hirsch, DS, Sasiela, CA, Wu, WJ

J Biol Chem 2008
22715382 Reduced surface expression of epithelial E-cadherin evoked by interferon-gamma is Fyn kinase-dependent

Smyth, D, Leung, G, Fernando, M, McKay, DM

PLoS One 2012
19711372 An acidic extracellular pH disrupts adherens junctions in HepG2 cells by Src kinases-dependent modification of E-cadherin

Chen, Y, Chen, CH, Tung, PY, Huang, SH, Wang, SM

J Cell Biochem 2009
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Orthologous Events
Ubiquitinated CDH1 translocates to lysosomes for degradation (Bos taurus)
Ubiquitinated CDH1 translocates to lysosomes for degradation (Canis familiaris)
Ubiquitinated CDH1 translocates to lysosomes for degradation (Danio rerio)
Ubiquitinated CDH1 translocates to lysosomes for degradation (Gallus gallus)
Ubiquitinated CDH1 translocates to lysosomes for degradation (Mus musculus)
Ubiquitinated CDH1 translocates to lysosomes for degradation (Rattus norvegicus)
Ubiquitinated CDH1 translocates to lysosomes for degradation (Sus scrofa)
Authored
Orlic-Milacic, M  (2025-01-10)
Reviewed
Raptis, L  (2025-11-21)
Created
Orlic-Milacic, M  (2025-01-15)
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