Genome-wide identification and gene expression profiling of ubiquitin ligases for endoplasmic reticulum protein degradation

Masayuki Kaneko, Ikuko Iwase, Yuki Yamasaki, Tomoko Takai, Yan Wu, Soshi Kanemoto, Koji Matsuhisa, Rie Asada, Yasunobu Okuma, Takeshi Watanabe, Kazunori Imaizumi, Yausyuki Nomura

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism by which unfolded proteins that accumulate in the ER are transported to the cytosol for ubiquitin-proteasome-mediated degradation. Ubiquitin ligases (E3s) are a group of enzymes responsible for substrate selectivity and ubiquitin chain formation. The purpose of this study was to identify novel E3s involved in ERAD. Thirty-seven candidate genes were selected by searches for proteins with RING-finger motifs and transmembrane regions, which are the major features of ERAD E3s. We performed gene expression profiling for the identified E3s in human and mouse tissues. Several genes were specifically or selectively expressed in both tissues; the expression of four genes (RNFT1, RNF185, CGRRF1 and RNF19B) was significantly upregulated by ER stress. To determine the involvement of the ER stress-responsive genes in ERAD, we investigated their ER localisation, in vitro autoubiquitination activity and ER stress resistance. All were partially localised to the ER, whereas CGRRF1 did not possess E3 activity. RNFT1 and RNF185, but not CGRRF1 and RNF19B, exhibited significant resistance to ER stressor in an E3 activity-dependent manner. Thus, these genes are possible candidates for ERAD E3s.

Original languageEnglish
Article number30955
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Aug 3 2016

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Genome-wide identification and gene expression profiling of ubiquitin ligases for endoplasmic reticulum protein degradation'. Together they form a unique fingerprint.

Cite this