SUMO modification regulates the transcriptional activity of FLASH.

Abstract:

: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.

authors

Alm-Kristiansen AH,Norman IL,Matre V,Gabrielsen OS

doi

10.1016/j.bbrc.2009.07.053

subject

Has Abstract

pub_date

2009-09-25 00:00:00

pages

494-9

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)01397-7

journal_volume

387

pub_type

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