Many sources of stress cause accumulation of unfolded or misfolded proteins in endoplasmic reticulum(ER), which elicits the unfolded protein response(UPR) to either promote cell survival or programmed cell death depen...Many sources of stress cause accumulation of unfolded or misfolded proteins in endoplasmic reticulum(ER), which elicits the unfolded protein response(UPR) to either promote cell survival or programmed cell death depending on different developmental context or stress severity. The Arabidopsis membrane-associated transcription factor, b ZIP28, is the functional equivalent of mammalian ATF6, which relocates from the ER to the Golgi where it is proteolytically processed and released from the membrane to the nucleus to mediate the UPR. Although the canonical site-1 protease(S1P) cleavage site on the ER lumen-facing domain is well conserved between b ZIP28 and ATF6, the importance of S1 P cleavage on b ZIP28 has not been experimentally demonstrated. Here we provide genetic evidence that the RRIL573 site, but not the RVLM373 site, on the lumen-facing domain of bZ IP28 is critical for the biological function of b ZIP28 under ER stress condition. Further biochemistry and cell biology studies demonstrated that the RRIL573 site, but not the RVLM373 site, is required for proteolytic processing and nuclear relocation of b ZIP28 in response to ER stress. Our results reveal that S1 P cleavage site plays a pivotal role in activation and function of b ZIP28 during UPR in plants.展开更多
基金supported by grants from the National Basic Research Program of China(973 Program,2012CB910500)the National Natural Science Foundation of China(31171157,31222008)the Specialized Research Fund for the Doctoral Program of Higher Education(20130071110011)
文摘Many sources of stress cause accumulation of unfolded or misfolded proteins in endoplasmic reticulum(ER), which elicits the unfolded protein response(UPR) to either promote cell survival or programmed cell death depending on different developmental context or stress severity. The Arabidopsis membrane-associated transcription factor, b ZIP28, is the functional equivalent of mammalian ATF6, which relocates from the ER to the Golgi where it is proteolytically processed and released from the membrane to the nucleus to mediate the UPR. Although the canonical site-1 protease(S1P) cleavage site on the ER lumen-facing domain is well conserved between b ZIP28 and ATF6, the importance of S1 P cleavage on b ZIP28 has not been experimentally demonstrated. Here we provide genetic evidence that the RRIL573 site, but not the RVLM373 site, on the lumen-facing domain of bZ IP28 is critical for the biological function of b ZIP28 under ER stress condition. Further biochemistry and cell biology studies demonstrated that the RRIL573 site, but not the RVLM373 site, is required for proteolytic processing and nuclear relocation of b ZIP28 in response to ER stress. Our results reveal that S1 P cleavage site plays a pivotal role in activation and function of b ZIP28 during UPR in plants.
