SUMO modification regulates the transcriptional activity of FLASH

被引：14

作者：

Alm-Kristiansen, Anne Hege ^{[1
]}

Norman, Ingrid Louise ^{[1
]}

Matre, Vilborg ^{[1
]}

Gabrielsen, Odd Stokke ^{[1
]}

机构：

[1] Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 387卷 / 03期

关键词：

FLASH; CASP8AP2; Ubc9; SUMO-1; SENP1; Transcription; GLUCOCORTICOID-RECEPTOR; NUCLEAR-BODIES; BINDING; SUMOYLATION; PROTEINS; COACTIVATOR; ACTIVATION; APOPTOSIS; INTERACTS; PATHWAY;

D O I：

10.1016/j.bbrc.2009.07.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

FLASH is a huge multifunctional nuclear protein that has been linked to apoptotic signalling, transcriptional control and Cajal body function. To gain further insight into the functions of the FLASH protein, we performed a yeast two-hybrid screening with FLASH as bait and identified the SUMO-conjugating enzyme Ubc9 as an interaction partner. The main interaction Surface for Ubc9 was found in the C-terminal part of FLASH, which is also a target for sumoylation. We identified K1813 as the major sumoylation site in FLASH, being enhanced by the SUMO E3 ligases Pc2 and PIASy. Disruption of this SUMO-conjugation site did not change the speckled subnuclear localization of FLASH, but it caused a reduction in FLASH activity as measured in a Gal4-tethering assay. Interestingly, the SUMO-specific protease SENP1 activated FLASH in the same assay. Overall, our results point to a complex involvement of sumoylation ill Modulating the function of FLASH. (C) 2009 Elsevier Inc. All rights reserved

引用

页码：494 / 499

页数：6

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