IRE1α-XBP1 is a novel branch in the transcriptional regulation of Ucp1 in brown adipocytes

被引：32

作者：

Asada, Rie ^{[1
]}

Kanemoto, Soshi ^{[1
]}

Matsuhisa, Koji ^{[1
]}

Hino, Kenta ^{[1
]}

Cui, Min ^{[1
]}

Cui, Xiang ^{[1
]}

Kaneko, Masayuki ^{[1
]}

Imaizumi, Kazunori ^{[1
]}

机构：

[1] Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Biochem, Minami Ku, Hiroshima 7348553, Japan

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

日本学术振兴会;

关键词：

UNFOLDED PROTEIN RESPONSE; RETICULUM STRESS-RESPONSE; ENDOPLASMIC-RETICULUM; ADIPOSE-TISSUE; ER STRESS; TRANSMEMBRANE PROTEIN; TRANSDUCER OASIS; GENE-EXPRESSION; INDUCTION; ACTIVATION;

D O I：

10.1038/srep16580

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The unfolded protein response (UPR) not only resolves endoplasmic reticulum (ER) stress, but also regulates cellular physiological functions. In this study, we first linked the UPR to the physiological roles of brown adipose tissue (BAT). BAT is one of the tissues that control energy homeostasis in the body. Brown adipocytes are able to dissipate energy in the form of heat owing to their mitochondrial protein, uncoupling protein 1 (UCP1). We found that one of the UPR branches, the IRE1 alpha-XBP1 pathway, was activated during the transcriptional induction of Ucp1. Inhibiting the IRE1 alpha-XBP1 pathway reduced the induction of Ucp1 expression. However, the activation of the IRE1 alpha-XBP1 pathway by ER stress never upregulated Ucp1. On the other hand, the activation of protein kinase A (PKA) induced Ucp1 transcription through the activation of IRE1 alpha-XBP1. The inhibition of PKA abrogated the activation of IRE1 alpha-XBP1 pathway, while the inhibition of a p38 mitogen activated protein kinase (p38 MAPK), which is one of the downstream molecules of PKA, never suppressed the activation of IRE1 alpha-XBP1 pathway. These data indicate that PKA-dependent IRE1 alpha-XBP1 activation is crucial for the transcriptional induction of Ucp1 in brown adipocytes, and they demonstrate a novel, ER stress -independent role of the UPR during thermogenesis.

引用

页数：12

共 51 条

[11] Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase [J].