E3 ubiquitin-protein ligase Hakai (CBLL1)

E3 ubiquitin-protein ligase Hakai (CBLL1) is a RING finger E3 ligase that selectively ubiquitinates tyrosine-phosphorylated E-cadherin and other substrates, targeting them for endocytosis and lysosomal degradation. By regulating E-cadherin stability, CBLL1 plays a central role in controlling epithelial cell–cell adhesion, epithelial–mesenchymal transition, and associated processes such as proliferation, migration, and invasion. CBLL1 is implicated in the progression of cancers characterized by reduced cell adhesion and increased invasiveness. It may also participate in cellular RNA methylation through its role in the WMM complex. The gene is considered a potential oncogenic factor, but there are no current drugs approved that specifically target CBLL1’s activity.

Other names

HakaiRNF188Cbl proto-oncogene like 1Casitas B-lineage lymphoma-transforming sequence-like protein 1RING-type E3 ubiquitin transferase HakaiE3 ubiquitin-protein ligase HakaiE3 ubiquitin protein ligaseE-cadherin binding protein E7Cas-Br-M (murine) ecotropic retroviral transforming sequence-like 1

Inhibition of CBLL1/Hakai may stabilize E-cadherin and suppress cell invasiveness (theoretical, no approved specific drugs) Targeting its E3 ligase activity could affect cell adhesion and tumor progression