The Rsp5 ubiquitin ligase and the AAA-ATPase Cdc48 control the ubiquitin-mediated degradation of the COPII component Sec23.
Ubp3/Bre5 complex is a substrate-specific deubiquitylating enzyme which mediates deubiquitylation of Sec23, a component of the COPII complex involved in the transport between endoplasmic reticulum and Golgi apparatus. Here we show that ubiquitylation of Sec23 is controlled by the Rsp5 ubiquitin ligase both in vivo and in vitro. We have recently identified Cdc48, a chaperone-like that plays a key role in the proteasomal escort pathway, as a partner of the Ubp3/Bre5 complex. We now found that cdc48 thermosensitive mutant cells not only accumulate ubiquitylated form of Sec23 but also display a stabilization of this protein at the restrictive temperature. This indicates that Cdc48 controls the proteasome-mediated degradation of Sec23. Our data favor the idea that Cdc48 plays a key role in deciphering fates of ubiquitylated Sec23 to degradation or deubiquitylation/stabilization via its cofactors.
Ossareh-Nazari
Batool
B
Institut Jacques Monod, Université Paris VII, CNRS, Bâtiment Buffon, Paris, France.
Cohen
Mickaël
M
Dargemont
Catherine
C
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D022181:COP-Coated Vesicles / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology; D000074405:Valosin Containing Protein; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D020690:GTPase-Activating Proteins; C512636:HRP1 protein, S cerevisiae; C104361:NPL4 protein, S cerevisiae; D029543:Nucleocytoplasmic Transport Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C079037:SEC23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D039221:mRNA Cleavage and Polyadenylation Factors; C501306:Ubc4 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D010450:Endopeptidases; C503886:Bre5 protein, S cerevisiae; C101111:UBP3 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein; D044764:Ubiquitin-Activating Enzymes; C469287:RSP5 protein, S cerevisiae