Details

Autor(en) / Beteiligte

• Matsunaga, Ryota
• Nishino, Tasuku
• Yokoyama, Atsushi
• Nakashima, Akio
• Kikkawa, Ushio
• Konishi, Hiroaki

Titel

Versatile function of the circadian protein CIPC as a regulator of Erk activation

Ist Teil von

• Biochemical and biophysical research communications, 2016-01, Vol.469 (3), p.377-383

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The CLOCK-interacting protein, Circadian (CIPC), has been identified as an additional negative-feedback regulator of the circadian clock. However, recent study on CIPC knockout mice has shown that CIPC is not critically required for basic circadian clock function, suggesting other unknown biological roles for CIPC. In this study, we focused on the cell cycle dependent nuclear-cytoplasmic shuttling function of CIPC and on identifying its binding proteins. Lys186 and 187 were identified as the essential amino acid residues within the nuclear localization signal (NLS) of CIPC. We identified CIPC-binding proteins such as the multifunctional enzyme CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase), which is a key enzyme for de novo pyrimidine synthesis. Compared to control cells, HEK293 cells overexpressing wild-type CIPC showed suppressed cell proliferation and retardation of cell cycle. We also found that PMA-induced Erk activation was inhibited with expression of wild-type CIPC. In contrast, the NLS mutant of CIPC, which reduced the ability of CIPC to translocate into the nucleus, did not exhibit these biological effects. Since CAD and Erk have significant roles in cell proliferation and cell cycle, CIPC may work as a cell cycle regulator by interacting with these binding proteins. •CIPC is a cell cycle dependent nuclear-cytoplasmic shuttling protein.•K186 and 187are the essential amino acid residues within the NLS of CIPC.•CAD was identified as a novel CIPC-binding protein.•CIPC might regulate the activity and translocation of CAD in the cells.