Nik‐related kinase is targeted for proteasomal degradation by the chaperone‐dependent ubiquitin ligase CHIP
| Autor: | Satomi Naito, Akinori Endo, Toshiaki Fukushima, Kimitoshi Denda, Masayuki Komada |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Proteasome Endopeptidase Complex
Immunoprecipitation Ubiquitin-Protein Ligases Biophysics Protein Serine-Threonine Kinases Biochemistry Substrate Specificity 03 medical and health sciences Ubiquitin Structural Biology Genetics Humans Molecular Biology Protein kinase B Heat-Shock Proteins 030304 developmental biology 0303 health sciences biology urogenital system Kinase Chemistry 030302 biochemistry & molecular biology Intracellular Signaling Peptides and Proteins Ubiquitination Purine Nucleosides Cell Biology equipment and supplies Cell biology Hsp70 Ubiquitin ligase HEK293 Cells Proteostasis Chaperone (protein) Proteolysis biology.protein Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists HeLa Cells Signal Transduction |
| Zdroj: | FEBS Letters. 594:1778-1786 |
| ISSN: | 1873-3468 0014-5793 |
| DOI: | 10.1002/1873-3468.13769 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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