Premium
Protein interaction screening identifies SH 3 RF 1 as a new regulator of FAT 1 protein levels
Author(s) -
Bock Charles E.,
Hughes Michael R.,
Snyder Kimberly,
Alley Steven,
Sadeqzadeh Elham,
Dun Matt D.,
McNagny Kelly M.,
Molloy Timothy J.,
Hondermarck Hubert,
Thorne Rick F.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12569
Subject(s) - ubiquitin ligase , regulator , microbiology and biotechnology , biology , ubiquitin , cadherin , signal transducing adaptor protein , cytoplasm , signal transduction , genetics , cell , gene
Mutations and ectopic FAT 1 cadherin expression are implicated in a broad spectrum of diseases ranging from developmental disorders to cancer. The regulation of FAT 1 and its downstream signalling pathways remain incompletely understood. We hypothesized that identification of additional proteins interacting with the FAT 1 cytoplasmic tail would further delineate its regulation and function. A yeast two‐hybrid library screen carried out against the juxtamembrane region of the cytoplasmic tail of FAT 1 identified the E3 ubiquitin‐protein ligase SH 3 RF 1 as the most frequently recovered protein‐binding partner. Ablating SH 3 RF 1 using si RNA increased cellular FAT 1 protein levels and stabilized expression at the cell surface, while overexpression of SH 3 RF 1 reduced FAT 1 levels. We conclude that SH 3 RF 1 acts as a negative post‐translational regulator of FAT 1 levels.