The COP1 E3-ligase interacts with FIP200, a key regulator of mammalian autophagy

Saori Kobayashi,Noriko Yoneda-Kato,Akihiro Yoshida,Jun-Ya Kato,Nagisa Itahara

doi:10.1186/1471-2091-14-1

Saori Kobayashi, Noriko Yoneda-Kato + Show 3 more

Open Access

https://doi.org/10.1186/1471-2091-14-1

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Abstract

BackgroundThe ubiquitin ligase COP1, COnstitutively Photomorphogenic 1, functions in many biological responses in mammalian cells, but its downstream pathway remains unclear.ResultsHere, we identified FIP200, a key regulator of mammalian autophagy, as a novel COP1-interacting protein by yeast two-hybrid screening. The interaction was confirmed by a GST-pulldown assay. Split-GFP analysis revealed that interaction between COP1 and FIP200 predominantly occurred in the cytoplasm and was enhanced in cells treated with UV irradiation. Different forms of FIP200 protein were expressed in cultured mammalian cells, and ectopic expression of COP1 reduced one of such forms.ConclusionsThese data suggest that COP1 modulates FIP200-associated activities, which may contribute to a variety of cellular functions that COP1 is involved in.

Highlights

The ubiquitin ligase COP1, COnstitutively Photomorphogenic 1, functions in many biological responses in mammalian cells, but its downstream pathway remains unclear
COP1 was identified as one of the COP proteins that act as a repressor of photomorphogenesis [1], and functions downstream of the COP9 signalosome complex [1,2,3] as a component of a multimeric E3 ubiquitin ligase complex that includes Cullin 4 (CUL4), Damaged DNA-Binding Protein 1 (DDB1), RING-Box 1 (RBX1), and Suppressor of Phya (SPA) proteins [4]
Identification of FIP200 as an interactor with COP1 To explore the novel signaling pathway mediated by COP1, we sought a candidate for interactors with COP1 by yeast two-hybrid screening of the human K562 erythroleukemia cDNA library

Summary

Introduction

The ubiquitin ligase COP1, COnstitutively Photomorphogenic 1, functions in many biological responses in mammalian cells, but its downstream pathway remains unclear. COP1 was identified as one of the COP proteins that act as a repressor of photomorphogenesis [1], and functions downstream of the COP9 signalosome complex [1,2,3] as a component of a multimeric E3 ubiquitin ligase complex that includes Cullin 4 (CUL4), Damaged DNA-Binding Protein 1 (DDB1), RING-Box 1 (RBX1), and Suppressor of Phya (SPA) proteins [4]. The mammalian ULK1(Atg1)-Atg13-FIP200(Atg17) complex functions downstream of mTOR, and, together with the Beclin 1-Vps kinase pathway and the Atg5-Atg and LC3 conjugation systems, plays a key role in the induction of autophagy, an intracellular lysosomal degradation system for cytoplasmic proteins and organelles [19,20,21,22,23]

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