SUMO modification regulates the transcriptional activity of FLASH

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-conjuga...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-09, Vol.387 (3), p.494-499
Main Authors: Alm-Kristiansen, Anne Hege, Norman, Ingrid Louise, Matre, Vilborg, Gabrielsen, Odd Stokke
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
CASP8AP2
Cell Nucleus - metabolism
ENZYMES
FLASH
GENE REGULATION
Humans
HYBRIDIZATION
Lysine - genetics
Lysine - metabolism
Protein Processing, Post-Translational
SCREENING
SENP1
Small Ubiquitin-Related Modifier Proteins - metabolism
SUMO-1
TRANSCRIPTION
Transcription, Genetic
Two-Hybrid System Techniques
Ubc9
Ubiquitin-Conjugating Enzymes - metabolism
YEASTS
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Summary: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 in modulating the function of FLASH.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.07.053