The TFIIH subunit Tfb3 regulates cullin neddylation

Gwenael Rabut, Gaelle Le Dez, Rati Verma, Taras Makhnevych, Axel Knebel, Thimo Kurz, Charles Boone, Raymond J. Deshaies, Matthias Peter

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    30 Citations (Scopus)

    Abstract

    Cullin proteins are scaffolds for the assembly of multisubunit ubiquitin ligases, which ubiquitylate a large number of proteins involved in widely varying cellular functions. Multiple mechanisms cooperate to regulate cullin activity, including neddylation of their C-terminal domain. Interestingly, we found that the yeast Cul4-type cullin Rtt101 is not only neddylated but also ubiquitylated, and both modifications promote Rtt101 function in vivo. Surprisingly, proper modification of Rtt101 neither correlated with catalytic activity of the RING domain of Hrt1 nor required the Nedd8 ligase Dcn1. Instead, ubiquitylation of Rtt101 was dependent on the ubiquitin-conjugating enzyme Ubc4, while efficient neddylation involves the RING domain protein Tfb3, a subunit of the transcription factor TFIIH. Tfb3 also controls Cul3 neddylation and activity in vivo, and physically interacts with Ubc4 and the Nedd8-conjugating enzyme Ubc12 and the Hrt1/Rtt101 complex. Together, these results suggest that the conserved RING domain protein Tfb3 controls activation of a subset of cullins.

    Original languageEnglish
    Pages (from-to)488-495
    Number of pages8
    JournalMolecular Cell
    Volume43
    Issue number3
    DOIs
    Publication statusPublished - 5 Aug 2011

    Keywords

    • RNA-POLYMERASE-II
    • NUCLEOTIDE EXCISION-REPAIR
    • TRANSCRIPTION FACTOR IIH
    • SACCHAROMYCES-CEREVISIAE
    • UBIQUITIN LIGASES
    • E3 LIGASE
    • IN-VIVO
    • PROTEIN
    • DNA
    • NEDD8

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