Tanaka Toshiaki, Iino Mitsuyoshi
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.
Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.
Cell Signal. 2014 Oct;26(10):2071-85. doi: 10.1016/j.cellsig.2014.06.003. Epub 2014 Jun 18.
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.
p27在细胞增殖和迁移中起重要作用，p27表达降低或出现胞质定位与多种人类肿瘤的不良临床预后相关。Jun激活域结合蛋白（Jab1）/组成型光形态建成蛋白9信号体5（CSN5）直接与p27相互作用，促进其易位和胞质降解。Sec6是外泌体复合体的一个组分。最近，多项研究表明Sec6在迁移、黏附和细胞分化中具有特定功能。然而，Sec6如何参与细胞周期进程的调控尚不清楚。本研究表明，Sec6通过使p27的苏氨酸157位点磷酸化来调节p27的胞质易位，从而通过与Jab1和Siah1相互作用促进p27在胞质中的降解，并抑制细胞周期进程。
