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Nik‐related kinase is targeted for proteasomal degradation by the chaperone‐dependent ubiquitin ligase CHIP
Author(s) -
Naito Satomi,
Fukushima Toshiaki,
Endo Akinori,
Denda Kimitoshi,
Komada Masayuki
Publication year - 2020
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 - 10.1002/1873-3468.13769
Subject(s) - ubiquitin ligase , immunoprecipitation , protein kinase b , ubiquitin , hsp70 , chaperone (clinical) , microbiology and biotechnology , hsp90 , chemistry , phosphorylation , heat shock protein , protein degradation , biology , biochemistry , gene , pathology , medicine
Nik‐related kinase (Nrk) is a member of the germinal center kinase IV family and suppresses Akt signaling. In vivo , Nrk prevents placental hyperplasia and breast cancer formation. Here, we show that Nrk is regulated by the chaperone‐dependent ubiquitin ligase carboxyl terminus of heat‐shock protein (Hsp)70‐interacting protein (CHIP). Immunoprecipitation and liquid chromatography–tandem mass spectrometry analysis reveal that Nrk preferentially interacts with CHIP and Hsp70/90 family proteins. Nrk protein levels are decreased by CHIP overexpression and increased by siRNA‐mediated CHIP knockdown. Our results indicate that Nrk is ubiquitinated by CHIP in a chaperone‐dependent manner, resulting in its proteasomal degradation. CHIP targets a fraction of Nrk molecules that have lost the ability to regulate Akt signaling. We conclude that CHIP plays an important role in regulating Nrk protein levels.