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PMID:14987998

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Citation

Häkli, M, Lorick, KL, Weissman, AM, Jänne, OA and Palvimo, JJ (2004) Transcriptional coregulator SNURF (RNF4) possesses ubiquitin E3 ligase activity. FEBS Lett. 560:56-62

Abstract

SNURF/RNF4 has been implicated in transcriptional regulation and growth inhibition in a RING finger-dependent fashion. In this work, we show that SNURF mediates its own ubiquitination in vitro in a ubiquitin-conjugating enzyme (E2)-selective manner: SNURF acts as an E3 ligase with UbcH5A and B, HHR6B (RAD6B), E2-25K, MmUbc7 and UbcH13, but not with UbcH3, UbcM4, MmUbc6 or E2-20K. In contrast, the well-characterized RING E3, AO7, functions only with members of the UbcH5 family. Furthermore, depending on the E2 used, the ubiquitin modification manifests as mono- or multi-ubiquitination. Mutation of conserved cysteine residues within the RING finger motif of SNURF abolishes the ubiquitination in vitro and in intact cells. Size fractionation of murine embryonal carcinoma F9 cell proteins shows that the majority of endogenous SNURF resides in salt-resistant > or =500-kDa complexes, suggesting that SNURF functions as a RING component in a multiprotein complex. Taken together, SNURF/RNF4 functions as an E3 ligase and this activity is closely linked to its transcription regulatory functions.

Links

PubMed Online version:10.1016/S0014-5793(04)00070-5

Keywords

Amino Acid Motifs; Animals; COS Cells; Cell Line, Tumor; Cercopithecus aethiops; Chromatography, Gel; Cysteine/metabolism; Glutathione/metabolism; Ligases/genetics; Ligases/metabolism; Mice; Point Mutation; Precipitin Tests; Recombinant Fusion Proteins/metabolism; Teratocarcinoma; Transcription, Genetic; Transfection; Ubiquitin/metabolism; Ubiquitin-Protein Ligases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:RNF4

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:RNF4

involved_in

GO:0016567: protein ubiquitination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:RNF4

involved_in

GO:0051865: protein autoubiquitination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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