Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the ubiquitin ligase HERC2.
J Biol Chem
; 289(28): 19789-98, 2014 Jul 11.
Article
de En
| MEDLINE
| ID: mdl-24855649
ABSTRACT
Because the deubiquitinating enzyme USP33 is involved in several important cellular processes (ß-adrenergic receptor recycling, centrosome amplification, RalB signaling, and cancer cell migration), its levels must be carefully regulated. Using quantitative mass spectrometry, we found that the intracellular level of USP33 is highly sensitive to the activity of p97. Knockdown or chemical inhibition of p97 causes robust accumulation of USP33 due to inhibition of its degradation. The p97 adaptor complex involved in this function is the Ufd1-Npl4 heterodimer. Furthermore, we identified HERC2, a HECT domain-containing E3 ligase, as being responsible for polyubiquitination of USP33. Inhibition of p97 causes accumulation of polyubiquitinated USP33, suggesting that p97 is required for postubiquitination processing. Thus, our study has identified several key molecules that control USP33 degradation within the ubiquitin-proteasome system.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Adenosine triphosphatases
/
Protéines du cycle cellulaire
/
Facteurs d'échange de nucléotides guanyliques
/
Ubiquitin thiolesterase
/
Ubiquitination
/
Protéolyse
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Biol Chem
Année:
2014
Type de document:
Article