title: Characterization of amino acid residues within the N-terminal region of Ubc9 that play a role in Ubc9 nuclear localization.
abstract: As the sole E2 enzyme for SUMOylation, Ubc9 is predominantly nuclear. However, the underlying mechanisms of Ubc9 nuclear localization are still not well understood. Here we show that RNAi-depletion of Imp13, an importin known to mediate Ubc9 nuclear import, reduces both Ubc9 nuclear accumulation and global SUMOylation. Furthermore, Ubc9-R13A or Ubc9-H20D mutation previously shown to interrupt the interaction of Ubc9 with nucleus-enriched SUMOs reduces the nuclear enrichment of Ubc9, suggesting that the interaction of Ubc9 with the nuclear SUMOs may enhance Ubc9 nuclear retention. Moreover, Ubc9-R17E mutation, which is known to disrupt the interaction of Ubc9 with both SUMOs and Imp13, causes a greater decrease in Ubc9 nuclear accumulation than Ubc9-R13A or Ubc9-H20D mutation. Lastly, Ubc9-K74A/S89D mutations that perturb the interaction of Ubc9 with nucleus-enriched SUMOylation-consensus motifs has no effect on Ubc9 nuclear localization. Altogether, our results have elucidated that the amino acid residues within the N-terminal region of Ubc9 play a pivotal role in regulation of Ubc9 nuclear localization.
authors: Department of Biological Sciences, Wayne State University, 5947 Gullen Mall, Detroit, MI 48202, USA.
authors: Palak
authors: P
authors: Sekhri
authors: School of Life Sciences, Xiamen University, Xiamen, China.
authors: Tao
authors: T
authors: Tao
authors: Department of Human Genetics, McGill University, Montreal, Canada.
authors: Feige
authors: F
authors: Kaplan
authors: Department of Biological Sciences, Wayne State University, 5947 Gullen Mall, Detroit, MI 48202, USA. Electronic address: xzhang@wayne.edu.
authors: Xiang-Dong
authors: XD
authors: Zhang
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D034622:RNA Interference; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C527880:IPO13 protein, human; D028884:Karyopherins; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: Importin 13; Nuclear import; Nuclear localization; Nuclear retention; SUMOylation; Ubc9