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Details on Person CBLL1 (Hakai)-ubiquitinated CDH1 (E-cadherin) is preferentia...

Class:IdSummation:9935573
_displayNameCBLL1 (Hakai)-ubiquitinated CDH1 (E-cadherin) is preferentia...
_timestamp2025-01-22 04:49:29
created[InstanceEdit:9935568] Orlic-Milacic, Marija, 2025-01-15
literatureReference[LiteratureReference:9935567] Distinct roles for cysteine cathepsin genes in multistage tumorigenesis
[LiteratureReference:9935106] Reduced surface expression of epithelial E-cadherin evoked by interferon-gamma is Fyn kinase-dependent
[LiteratureReference:9934839] An acidic extracellular pH disrupts adherens junctions in HepG2 cells by Src kinases-dependent modification of E-cadherin
[LiteratureReference:9935502] Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal growth factor receptor to Src-mediated pathway
[LiteratureReference:9935074] Competitive regulation of E-cadherin juxtamembrane domain degradation by p120-catenin binding and Hakai-mediated ubiquitination
[LiteratureReference:9935509] Lysosomal targeting of E-cadherin: a unique mechanism for the down-regulation of cell-cell adhesion during epithelial to mesenchymal transitions
[LiteratureReference:9935530] Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress
[LiteratureReference:9935578] Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
modified[InstanceEdit:9935576] Orlic-Milacic, Marija, 2025-01-15
[InstanceEdit:9935577] Orlic-Milacic, Marija, 2025-01-15
[InstanceEdit:9935583] Orlic-Milacic, Marija, 2025-01-16
[InstanceEdit:9936240] Orlic-Milacic, Marija, 2025-01-22
textCBLL1 (Hakai)-ubiquitinated CDH1 (E-cadherin) is preferentially, if not exclusively, degraded through the lysosomal route. Among lysosomal peptidases, cathepsin B (CTSB), cathepsin L (CTSL), and cathepsin S (CTSS) were reported to be involved in lysosomal degradation of CDH1 based on in vivo studies with cathepsin gene knockouts in a mouse model of pancreatic islet carcinogenesis and in vitro assays using recombinant human CDH1 and recombinant human CTSB, CTSL, and CTSS (Gocheva et al. 2006). Expression of these cathepsins is elevated in mouse pancreatic endocrine tumors, and knockout of individual cathepsin genes reduces tumor invasiveness (Gocheva et al. 2006). Human pancreatic endocrine tumors frequently overexpress CTSB and CTSL and expression levels of these cathepsins correlate with malignancy (Gocheva et al. 2006). Lysosomal degradation of a recombinant mouse CDH1 (E-cadherin) was reported 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) promotes 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 was reported to facilitate 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 promotes lysosomal localization and degradation of CDH1 in HepG2 cells, with no significant proteasome involvement (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 the lysosome and the proteasome contribute to degradation of internalized CDH1 (Smyth et al. 2012). Using recombinant human proteins expressed in human colon adenocarcinoma cell line Caco-2 it was reported that the proteasome is responsible for cleavage of the cytosolic tail of endocytosed CDH1 at the JMD, which is a pre-requisite for the lysosomal degradation of the extracellular region of CDH1 (Sako-Kubota et al. 2014).
(summation)[BlackBoxEvent:9935547] Lysosomal degradation of ubiquitinated CDH1 [Homo sapiens]
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