title: Nucleus accumbens associated 1 is recruited within the promyelocytic leukemia nuclear body through SUMO modification.
abstract: Nucleus accumbens associated 1 (NACC1) is a cancer-associated BTB/POZ (pox virus and zinc finger/bric-a-brac tramtrack broad complex) gene, and is involved in several cellular functions in neurons, cancer and stem cells. Some of the BTB/POZ proteins associated with cancer biology are SUMOylated, which appears to play an important role in transcription regulation. We show that NACC1 is SUMOylated on a phylogenetically conserved lysine (K167) out of three consensus SUMOylation motif sites. Amino acid substitution in the SIM sequence (SIM/M) within the BTB/POZ domain partially reduced K167 SUMOylation activity of NACC1. Overexpression of GFP-NACC1 fusion protein leads to formation of discrete nuclear foci similar to promyelocytic leukemia nuclear bodies (PML-NB), which colocalized with SUMO paralogues (SUMO1/2/3). Both NACC1 nuclear body formation and colocalization with SUMO paralogues were completely suppressed in the GFP-NACC1-SIM/M mutant, whereas they were partially maintained in the NACC1 K167R mutant. Confocal immunofluorescence analysis showed that endogenous and exogenous NACC1 proteins colocalized with endogenous PML protein. A pull-down assay revealed that the consensus motifs of the SUMO acceptor site at K167 and the SIM within the BTB/POZ domain were both necessary for efficient binding to PML protein. Our study demonstrates that NACC1 can be modified by SUMO paralogues, and cooperates with PML protein.
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Japan.|Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tatemichi
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibazaki
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuhira
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Japan.
authors.forename: Shuya
authors.initials: S
authors.lastname: Kasai
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oikawa
authors.affiliation: Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takikawa
authors.affiliation: Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Japan.
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
mesh_terms: D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: Migration; SUMO-interacting motif; SUMOylations; nucleus accumbens associated 1; promyelocytic leukemia nuclear body