Bul proteins, a nonredundant, antagonistic family of ubiquitin ligase regulatory proteins.
Like other Nedd4 ligases, Saccharomyces cerevisiae E3 Rsp5p utilizes adaptor proteins to interact with some substrates. Previous studies have indentified Bul1p and Bul2p as adaptor proteins that facilitate the ligase-substrate interaction. Here, we show the identification of a third member of the Bul family, Bul3p, the product of two adjacent open reading frames separated by a stop codon that undergoes readthrough translation. Combinatorial analysis of BUL gene deletions reveals that they regulate some, but not all, of the cellular pathways known to involve Rsp5p. Surprisingly, we find that Bul proteins can act antagonistically to regulate the same ubiquitin-dependent process, and the nature of this antagonistic activity varies between different substrates. We further show, using in vitro ubiquitination assays, that the Bul proteins have different specificities for WW domains and that the two forms of Bul3p interact differently with Rsp5p, potentially leading to alternate functional outcomes. These data introduce a new level of complexity into the regulatory interactions that take place between Rsp5p and its adaptors and substrates and suggest a more critical role for the Bul family of proteins in controlling adaptor-mediated ubiquitination.
School of Biological and Chemical Sciences, Queen Mary, University of London, London, United Kingdom.
Tatiana V
TV
Novoselova
Kiran
K
Zahira
Ruth-Sarah
RS
Rose
James A
JA
Sullivan
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D026905:Amino Acid Transport Systems / Q000378:metabolism; D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D055786:Gene Knockout Techniques; D008565:Membrane Proteins / Q000378:metabolism; D050296:Microbial Viability / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; C502212:CAN1 protein, S cerevisiae; D027682:Cation Transport Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C491145:GAP1 protein, S cerevisiae; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C105116:SMF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; C469287:RSP5 protein, S cerevisiae