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Cep78 controls centrosome homeostasis by inhibiting EDD ‐ DYRK 2‐ DDB 1 Vpr BP
Author(s) -
Hossain Delowar,
Javadi Esfehani Yalda,
Das Arindam,
Tsang William Y
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201642377
Subject(s) - biology , centrosome , microbiology and biotechnology , centriole , ubiquitin , cell cycle , biochemistry , microtubule , cell , gene
The centrosome plays a critical role in various cellular processes including cell division and cilia formation, and deregulation of centrosome homeostasis is a hallmark feature of many human diseases. Here, we show that centrosomal protein of 78 kDa (Cep78) localizes to mature centrioles and directly interacts with viral protein R binding protein (Vpr BP ). Although Vpr BP is a component of two distinct E3 ubiquitin ligases, EDD ‐ DYRK 2‐ DDB 1 Vpr BP and CRL 4 Vpr BP , Cep78 binds specifically to EDD ‐ DYRK 2‐ DDB 1 Vpr BP and inhibits its activity. A pool of EDD ‐ DYRK 2‐ DDB 1 Vpr BP is active at the centrosome and mediates ubiquitination of CP 110, a novel centrosomal substrate. Deregulation of Cep78 or EDD ‐ DYRK 2‐ DDB 1 Vpr BP perturbs CP 110 ubiquitination and protein stability, thereby affecting centriole length and cilia assembly. Mechanistically, ubiquitination of CP 110 entails its phosphorylation by DYRK 2 and binding to Vpr BP . Cep78 specifically impedes the transfer of ubiquitin from EDD to CP 110 without affecting CP 110 phosphorylation and binding to Vpr BP . Thus, we identify Cep78 as a new player that regulates centrosome homeostasis by inhibiting the final step of the enzymatic reaction catalyzed by EDD ‐ DYRK 2‐ DDB 1 Vpr BP .