Journal
CELLULAR SIGNALLING
Volume 26, Issue 10, Pages 2071-2085Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2014.06.003
Keywords
Sec6; p27; Jun activation domain-binding protein 1; Seven in absentia homolog 1; Cell cycle arrest
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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. (C) 2014 Elsevier Inc. All rights reserved.
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