CBLL1 explained

The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene.^[1] This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation.

Function

Hakai functions as a RING finger domain-containing E3 ubiquitin ligase for E-cadherin. Hakai mediates E-cadherin ubiquitination and its degradation by proteasomes. "Hakai" means "destruction" in Japanese. Proteosomal degradation of E-cadherin can be regulated by phosphorylation. The Hakai binding site is a part of the E-cadherin cytoplasmic domain that contains several tyrosines.^[2] Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin.^[3] Two lysines of the E-cadherin cytoplasmic domain have been shown to be sites for ubiquitination.^[4] Hakai also interacts with polypyrimidine tract-binding protein-associated splicing factor.^[5]

See also

• CBL (gene)

the gene name "CBLL1" comes from "Cbl-like protein 1"

Notes and References

1. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W . Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex . Nature Cell Biology . 4 . 3 . 222–31 . Mar 2002 . 11836526 . 10.1038/ncb758 . 40423770 .
2. Aparicio LA, Valladares M, Blanco M, Alonso G, Figueroa A . Biological influence of Hakai in cancer: a 10-year review . Cancer and Metastasis Reviews . 31 . 1–2 . 375–86 . Jun 2012 . 22349934 . 3350634 . 10.1007/s10555-012-9348-x .
3. Mukherjee M, Chow SY, Yusoff P, Seetharaman J, Ng C, Sinniah S, Koh XW, Asgar NF, Li D, Yim D, Jackson RA, Yew J, Qian J, Iyu A, Lim YP, Zhou X, Sze SK, Guy GR, Sivaraman J . Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin . The EMBO Journal . 31 . 5 . 1308–19 . Mar 2012 . 22252131 . 3298002 . 10.1038/emboj.2011.496 .
4. Hartsock A, Nelson WJ . Competitive regulation of E-cadherin juxtamembrane domain degradation by p120-catenin binding and Hakai-mediated ubiquitination . PLOS ONE . 7 . 5 . e37476 . 2012 . 22693575 . 3365061 . 10.1371/journal.pone.0037476 . 2012PLoSO...737476H . free .
5. Figueroa A, Fujita Y, Gorospe M . Hacking RNA: Hakai promotes tumorigenesis by enhancing the RNA-binding function of PSF . Cell Cycle . 8 . 22 . 3648–51 . Nov 2009 . 19855157 . 2808762 . 10.4161/cc.8.22.9909 .