RGD Reference Report - RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. - Rat Genome Database

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RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation.

Authors: Tatham, MH  Geoffroy, MC  Shen, L  Plechanovova, A  Hattersley, N  Jaffray, EG  Palvimo, JJ  Hay, RT 
Citation: Tatham MH, etal., Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13.
RGD ID: 8553731
Pubmed: PMID:18408734   (View Abstract at PubMed)
DOI: DOI:10.1038/ncb1716   (Journal Full-text)

In acute promyelocytic leukaemia (APL), the promyelocytic leukaemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). This disease can be treated effectively with arsenic, which induces PML modification by small ubiquitin-like modifiers (SUMO) and proteasomal degradation. Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro. In the absence of RNF4, arsenic failed to induce degradation of PML and SUMO-modified PML accumulated in the nucleus. These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rnf4Ratprotein K11-linked ubiquitination involved_inIDA PMID:18408734UniProt 
Rnf4Ratprotein K48-linked ubiquitination involved_inIDA PMID:18408734UniProt 
Rnf4Ratprotein K6-linked ubiquitination involved_inIDA PMID:18408734UniProt 
Rnf4Ratprotein K63-linked ubiquitination involved_inIDA PMID:18408734UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rnf4RatSUMO polymer binding enablesIPIUniProtKB:P61956PMID:18408734UniProt 
Rnf4RatSUMO polymer binding enablesIPIUniProtKB:P63165PMID:18408734UniProt 
Rnf4RatSUMO polymer binding  IDA Sumo2RGD 
Rnf4Ratubiquitin-protein transferase activity enablesIDA PMID:18408734UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Rnf4  (ring finger protein 4)


Additional Information