title: Nuclear export inhibitor leptomycin B induces the appearance of novel forms of human Mdm2 protein.
abstract: The nuclear export inhibitor leptomycin B (LMB) prevents the export of proteins from the nucleus to the cytoplasm, protects p53 from Mdm2-mediated degradation and is a very potent inducer of the p53 transcriptional activity. Here we suggest that LMB can also interfere with the degradation of human Mdm2. In the presence of this drug, we observed two novel forms of this protein: a slow mobility form and an amino-terminal fragment with an apparent molecular mass of 32 kDa. The presence of this 32 kDa band is abolished with proteasome inhibitors, indicating that its appearance could be because of limited processing by the proteasome. These results may be useful in understanding the mechanism of degradation of Mdm2 by the proteasome.
authors.affiliation: Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: S
authors.initials: S
authors.lastname: Menéndez
authors.forename: M
authors.initials: M
authors.lastname: Higgins
authors.forename: R G
authors.initials: RG
authors.lastname: Berkson
authors.forename: C
authors.initials: C
authors.lastname: Edling
authors.forename: D P
authors.initials: DP
authors.lastname: Lane
authors.forename: S
authors.initials: S
authors.lastname: Laín
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C038753:leptomycin B