title: Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition.
abstract: We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus.
authors.affiliation: Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto, Japan.
authors.forename: Hotaru
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto, Japan; Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan. Electronic address: hisa@kumamoto-u.ac.jp.
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein / Q000032:analysis / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000032:analysis / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism; D025801:Ubiquitin / Q000032:analysis / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D007976:Leupeptins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D061988:Proteasome Inhibitors; C114070:RNF4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C070576:PML protein, human; D011691:Puromycin; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Nuclear protein sequestration; Promyelocytic leukemia nuclear bodies; Puromycin; Small ubiquitin-related modifier (SUMO); Ubiquitin proteasome system