GPNMB Induces BiP Expression by Enhancing Splicing of BiP Pre-mRNA during the Endoplasmic Reticulum Stress Response.
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| Abstract |
Glycoprotein nonmetastatic melanoma protein B (GPNMB) has a neuroprotective effect against neuronal cell death caused by the accumulation of abnormal mutated proteins. It is known that the accumulation of pathological proteins induces endoplasmic-reticulum (ER) stress leading to cell damage. The aim of this study was to determine the role of GPNMB in the ER stress response. GPNMB was greatly up-regulated by thapsigargin-induced ER stress. Under the ER stress conditions, GPNMB relocated to the nucleus and specifically up-regulated expression of BiP at the mRNA level by promoting the BiP pre-mRNA splicing, not through the pathways initiated by the three major transducers of the unfolded protein response: IRE1, PERK, and ATF6. Furthermore, we found that the protein level of BiP and the infarction were increased and attenuated, respectively, in Gpnmb-transgenic mice after occlusion of the middle cerebral artery, in comparison with wild-type mice. Thus, our findings indicate that GPNMB enhances the BiP expression by promoting the splicing (thereby preventing cell death caused by ER stress) and could be a therapeutic target in ER stress-related disorders.
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| Authors | Yasuhiro Noda, Kazuhiro Tsuruma, Masafumi Takata, Mitsue Ishisaka, Hirotaka Tanaka, Yusuke Nakano, Yuki Nagahara, Masamitsu Shimazawa, Hideaki Hara |
| Journal | Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 12160 (09 22 2017) ISSN: 2045-2322 [Electronic] England |
| PMID | 28939899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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