The E3 ubiquitin ligase HOIL-1 induces the polyubiquitination and degradation of SOCS6 associated proteins.
The suppressor of cytokine signaling (SOCS) proteins are thought to exert their function through the recruitment of interacting-proteins to the ubiquitin/proteasome degradation pathway. All SOCS proteins bind an Elongin BC E3 ubiquitin ligase complex through the common Socs-box. Here, we show that haem-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), another E3 ubiquitin ligase, interacts with SOCS6. The Ubl domain of HOIL-1 and the SH2 and Socs-box domains of SOCS6 are required for the interaction. HOIL-1 expression stabilizes SOCS6 and induces the ubiquitination and degradation of proteins associated with SOCS6. These data suggest that SOCS proteins may interact with different E3 ubiquitin ligases in addition to a common Elongin BC E3 complex.
Bayle
Julie
J
INSERM UMR599, Laboratoire d'hématopoïèse moléculaire et fonctionnelle, Marseille, France.
Lopez
Sophie
S
Iwaï
Kazuhiro
K
Dubreuil
Patrice
P
De Sepulveda
Paulo
P
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
C473086:Socs6 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C504507:RBCK1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex