title: Sec6 regulated cytoplasmic translocation and degradation of p27 via interactions with Jab1 and Siah1.
abstract: p27 has essential roles in cellular proliferation and migration, and reduced or cytoplasmic p27 is associated with poor clinical outcomes in a variety of human tumours. Jun activation domain-binding protein (Jab1)/constitutive photomorphogenic-9 signalosome 5 (CSN5) directly interacts with p27 promoting its translocation and cytoplasmic degradation. Sec6 is a component of the exocyst complex. Recently, several studies revealed that Sec6 has specific functions in migration, adhesion, and cell differentiation. However, how Sec6 is involved in the regulation of cell cycle progression is unknown. The present study shows that Sec6 regulates cytoplasmic translocation of p27 through p27 phosphorylation at Thr157, thereby promoting p27 degradation in the cytoplasm via interaction with Jab1 and Siah1 and suppressing cell cycle progression.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan; Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan. Electronic address: ttanaka@med.id.yamagata-u.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Iino
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014178:Translocation, Genetic; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D048948:14-3-3 Proteins; C490685:EXOC3 protein, human; C489607:EXOC4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex
keywords: Cell cycle arrest; Jun activation domain-binding protein 1; Sec6; Seven in absentia homolog 1; p27