Sec6 regulated cytoplasmic translocation and degradation of p27 via interactions with Jab1 and Siah1

Toshiaki Tanaka; Mitsuyoshi Iino

doi:10.1016/j.cellsig.2014.06.003

Sec6 regulated cytoplasmic translocation and degradation of p27 via interactions with Jab1 and Siah1

Cell Signal. 2014 Oct;26(10):2071-85. doi: 10.1016/j.cellsig.2014.06.003. Epub 2014 Jun 18.

Authors

Toshiaki Tanaka¹, Mitsuyoshi Iino²

Affiliations

¹ 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.
² Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.

PMID: 24949832
DOI: 10.1016/j.cellsig.2014.06.003

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.

Keywords: Cell cycle arrest; Jun activation domain-binding protein 1; Sec6; Seven in absentia homolog 1; p27.

MeSH terms

14-3-3 Proteins / chemistry
14-3-3 Proteins / metabolism
COP9 Signalosome Complex
Cell Cycle Checkpoints
Cell Line, Tumor
Cell Nucleus / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / chemistry
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Cytoplasm / metabolism*
Gene Expression Regulation
HEK293 Cells
Humans
Immunoprecipitation
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Nuclear Proteins / chemistry
Nuclear Proteins / metabolism*
Peptide Hydrolases / genetics
Peptide Hydrolases / metabolism*
Phosphorylation
Protein Binding
RNA Interference
RNA, Small Interfering / metabolism
Translocation, Genetic
Ubiquitin-Protein Ligases / chemistry
Ubiquitin-Protein Ligases / metabolism*
Vesicular Transport Proteins / antagonists & inhibitors
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism*

Substances

14-3-3 Proteins
EXOC3 protein, human
EXOC4 protein, human
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
RNA, Small Interfering
Vesicular Transport Proteins
Cyclin-Dependent Kinase Inhibitor p27
Ubiquitin-Protein Ligases
seven in absentia proteins
Peptide Hydrolases
COPS5 protein, human
COP9 Signalosome Complex