title: The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation.
abstract: The heterodimeric ubiquitin conjugating enzyme (E2) UBC13-UEV mediates polyubiquitylation through lysine 63 of ubiquitin (K63), rather than lysine 48 (K48). This modification does not target proteins for proteasome-dependent degradation. Searching for potential regulators of this variant polyubiquitylation we have identified four proteins, namely RNF8, KIA00675, KF1, and ZNRF2, that interact with UBC13 through their RING finger domains. These domains can recruit, in addition to UBC13, other E2s that mediate canonical (K48) polyubiquitylation. None of these RING finger proteins were known previously to recruit UBC13. For one of these proteins, RNF8, we show its activity as a ubiquitin ligase that elongates chains through either K48 or K63 of ubiquitin, and its nuclear co-localization with UBC13. Thus, our screening reveals new potential regulators of non-canonical polyubiquitylation.
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Plans
authors.forename: Johanna
authors.initials: J
authors.lastname: Scheper
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.forename: Noureddine
authors.initials: N
authors.lastname: Loukili
authors.forename: Yukio
authors.initials: Y
authors.lastname: Okano
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Thomson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; C486521:RNF8 protein, human; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D008239:Lysine