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Targeting HECT ‐type E3 ligases – insights from catalysis, regulation and inhibitors
Author(s) -
Fajner Valentina,
Maspero Elena,
Polo Simona
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 - 10.1002/1873-3468.12775
Subject(s) - ubiquitin , ubiquitin ligase , function (biology) , ubiquitin protein ligases , enzyme , microbiology and biotechnology , posttranslational modification , chemistry , substrate specificity , biochemistry , nedd4 , biology , gene
Ubiquitination plays a pivotal role in most cellular processes and is critical for protein degradation and signalling. E3 ligases are the matchmakers in the ubiquitination cascade, responsible for substrate recognition and modification with specific polyubiquitin chains. Until recently, it was not clear how the catalytic activity of E3s is modulated, but major recent studies on HECT E3 ligases is filling this void. These enzymes appear to be held in a closed, inactive conformation, which is relieved by biochemical manoeuvres unique to each member, thus ensuring exquisite regulation and specificity of the enzymes. The new advances and their significance to the function of HECT E3s are described here, with a particular focus on the Nedd4 family members.