Nucleobindin 1 controls the unfolded protein response by inhibiting ATF6 activation

作者：Tsukumo Yoshinori; Tomida Akihiro^*; Kitahara Osamu; Nakamura Yusuke; Asada Shinichi; Mori Kazutoshi; Tsuruo Takashi

来源：Journal of Biological Chemistry, 2007, 282(40): 29264-29272.

DOI：10.1074/jbc.M705038200

In response to endoplasmic reticulum (ER) stress, activating transcription factor 6 (ATF6), an ER membrane-anchored transcription factor, is transported to the Golgi apparatus and cleaved by site-1 protease (S1P) to activate the unfolded protein response (UPR). Here, we identified nucleobindin 1 (NUCB1) as a novel repressor of the S1P-mediated ATF6 activation. NUCB1 is an ER stress-inducible gene with the promoter region having functional cis-elements for transcriptional activation by ATF6. Overexpression of NUCB1 inhibits S1P-mediated ATF6 cleavage without affecting ER-to-Golgi transport of ATF6, whereas knock-down of NUCB1 by siRNA accelerates ATF6 cleavage during ER stress. NUCB1 protein localizes in the Golgi apparatus, and disruption of the Golgi localization results in loss of the ATF6-inhibitiory activity. Consistent with these observations, NUCB1 can suppress physical interaction of S1P-ATF6 during ER stress. Together, our results demonstrate that NUCB1 is the first-identified, Golgi-localized negative feedback regulator in the ATF6-mediated branch of the UPR.

• 出版日期2007-10-5
• 单位河北医科大学