Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.
Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.
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迄今为止，我们对X-Box结合蛋白1（XBP 1）在代谢过程中的作用的理解仅限于其上调ER折叠能力的能力，从而增加胰岛素敏感性。在这里，我们证明了XBP 1 s与叉头盒O 1（FoxO 1）转录因子相互作用，并指导其蛋白酶体介导的降解。我们的研究结果提供了第一个证据，除了对ER系统和胰岛素敏感性的调节作用外，XBP 1还可以通过与FoxO 1的相互作用独立调节葡萄糖稳态。事实上，XBP 1 s的DNA结合缺陷突变体，其不具有增加ER折叠能力的能力，仍然能够在严重肥胖和糖尿病ob/ob小鼠中降低血糖水平和增加葡萄糖耐量。XBP 1介导的FoxO 1降解可能会导致2型糖尿病治疗新方法的开发。
To date, our understanding of the role of X-Box Binding Protein 1 (XBP1) in metabolic processes was limited to its ability to up-regulate ER folding capacity and thereby, to increase insulin sensitivity. Here, we demonstrate that XBP1s interacts with Forkhead box O1 (FoxO1) transcription factor and directs it to proteasome-mediated degradation. Our results provide the first evidence that, in addition to its regulatory effects on the ER system and insulin sensitivity, XBP1s can independently regulate glucose homeostasis through its interaction with FoxO1. Indeed, a DNA binding defective mutant of XBP1s, which does not have the ability to increase ER folding capacity, is still capable of reducing blood glucose levels and increasing glucose tolerance in the severely obese and diabetic ob/ob mice. XBP1-mediated degradation of FoxO1 might lead to development of new therapeutic approaches for treatment of type 2 diabetes.
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影响因子：
29
作者：
Dong XC;Copps KD;Guo S;Li Y;Kollipara R;DePinho RA;White MF
通讯作者：
White MF
DOI：
10.1073/pnas.1002575107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Henis-Korenblit, Sivan;Zhang, Peichuan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
DOI：
10.1073/pnas.0406789102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Huang, H;Regan, KM;Tindall, DJ
通讯作者：
Tindall, DJ
影响因子：
16
作者：
Michael, MD;Kulkarni, RN;Kahn, CR
通讯作者：
Kahn, CR
DOI：
10.1073/pnas.0405454101
发表时间：
2004-09-14
影响因子：
11.1
作者：
Aoki, M;Hao, J;Vogt, PK
通讯作者：
Vogt, PK