Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP.
Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. We now demonstrate that HHARI also interacts with the eukaryotic mRNA cap binding protein, translation initiation factor 4E homologous protein (4EHP), via the N-terminal RING1 finger of HHARI. HHARI, 4EHP and UbcH7 do not form a stable heterotrimeric complex as 4EHP cannot immunoprecipitate UbcH7 even in the presence of HHARI. Overexpression of 4EHP and HHARI in mammalian cells leads to polyubiquitylation of 4EHP. By contrast, HHARI does not promote its own autoubiquitylation. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation.
Tan
Nancy G S
NG
Molecular Medicine Unit, Level 6, Clinical Sciences Building, St James's University Hospital, Leeds LS9 7TF, UK.
Ardley
Helen C
HC
Scott
Gina B
GB
Rose
Stephen A
SA
Markham
Alexander F
AF
Robinson
Philip A
PA
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; D039561:Eukaryotic Initiation Factor-4E; D016271:Proto-Oncogene Proteins c-myc; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; C419193:ARIH1 protein, human; D044767:Ubiquitin-Protein Ligases