SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation (The EMBO J, 2009, 28:2748-2762)

報告日期: 2010/03/16
報告時間: 16:00/16:50
報告學生: 任純儀(英文報告)
講評老師: 陳炳焜
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990316-2.pdf

SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation

 

Chao Huang, Yan Han, Yumei Wang, Xuxu Sun, Shan Yan, Edward TH Yeh, Yuying Chen, Hui Cang, Hui Li, Guiying Shi, Jinke Cheng, Xueming Tang and Jing Yi

 

The EMBO Journal 2009, 28:2748-2762

 

Speaker: 任純儀

Commentator: 陳炳焜 老師

Time: 2010/03/16 16:00-16:50

Place: Room 602

 

Abstract:

  Small ubiquitin-like modifier (SUMO) modification is one of post-translational protein modification. By conjugating and deconjugating SUMO modification, cells could regulate several cellular processes, such as cell signaling and nuclear transportation. To control cellular processes precisely, conjugation by SUMO ligases and deconjugation by SENPs (Sentrin/SUMO-specific proteases) are equally important. Though SUMO E1, E2 and E3 ligases have been explored by now, the mechanism of SENPs remains largely unknown. In this study, the authors found that mild ROS could stabilize and redistribute SENP3 to nucleoplasm where SENP3 could regulate nuclear events. Besides, the authors also found that HIF-1 (hypoxia-inducing factor-1) activation was correlated with SENP3 stabilization under mild oxidative stress. According to previous study, we knew that ROS could regulate HIF-1 activation by suppressing HIF-1α degradation1. Other than HIF-1α stabilization, SUMO conjugation/deconjugation was also known to play a role in HIF-1 activation2,3. The authors therefore tried to elucidate the role of SENP3 in HIF-1 activation under mild oxidative stress. These authors proved that de-SUMOylating activity of SENP3 is required for HIF-1 activation. However, to our surprise, SENP3 did not de-SUMOyalte HIF-1α but p300, one of the master co-activators of HIF-1α. Taken together, this important study unveiled another mechanism by which HIF-1 transactivation could be regulated by p300 de-SUMOylation under mild oxidative stress.

 

References:

1.     Gerald D, Berra E, Frapart YM, Chan DA, Giaccia AJ, Mansuy D, Pouyssegur J, Yaniv M and Mechta-Grigoriou F 2004. JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell. 118:781-794.

2.     Bae SH, Jeong JW, Park JA, Kim SH, Bae MK, Choi SJ and Kim KW 2004. Sumoylation increases HIF-1alpha stability and its transcriptional activity. Biochem Biophys Res Commun. 324:394-400

3.     Cheng J, Kang X, Zhang S and Yeh ET 2007. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell. 131:584-595