Chondrocyte Proliferation Regulated by Secreted Luminal Domain of ER Stress Transducer BBF2H7/CREB3L2

作者：Saito Atsushi; Kanemoto Soshi; Zhang Yizhou; Asada Rie; Hino Kenta; Imaizumi Kazunori^*

来源：Molecular Cell, 2014, 53(1): 127-139.

DOI：10.1016/j.molcel.2013.11.008

The endoplasmic reticulum (ER) stress transducer BBF2H7/CREB3L2 is an ER-resident transmembrane transcription factor. In response to physiological ER stress, it is processed at the transmembrane region to generate a cytoplasmic N terminus, which contains a basic leucine zipper (bZIP) domain, and luminal C terminus. The BBF2H7 N terminus functions as a transcription factor to promote the expression of ER-Golgi trafficking-related genes and plays crucial roles in chondrocyte differentiation. Here, we found that the BBF2H7 C terminus is secreted into the extracellular space as a signaling molecule for cell-to-cell communication. The secreted BBF2H7 C terminus directly binds to both Indian hedgehog and its receptor Patched-1, followed by activation of Hedgehog signaling, resulting in promoting the proliferation of neighboring chondrocytes. The dual N- and C-terminal functions of BBF2H7 triggered by physiological ER stress may allow chondrocytes to simultaneously regulate distinct cellular events for differentiation and proliferation in developing cartilage.

• 出版日期2014-1