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Molecular Cancer
Published in: Molecular Cancer 1/2011

Open Access 01-12-2011 | Research

PIAS1 interacts with FLASH and enhances its co-activation of c-Myb

Authors: Anne Hege Alm-Kristiansen, Petra I Lorenzo, Ann-Kristin Molværsmyr, Vilborg Matre, Marit Ledsaak, Thomas Sæther, Odd S Gabrielsen

Published in: Molecular Cancer | Issue 1/2011

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Abstract

Background

FLASH is a huge nuclear protein involved in various cellular functions such as apoptosis signalling, NF-κB activation, S-phase regulation, processing of histone pre-mRNAs, and co-regulation of transcription. Recently, we identified FLASH as a co-activator of the transcription factor c-Myb and found FLASH to be tightly associated with active transcription foci. As a huge multifunctional protein, FLASH is expected to have many interaction partners, some which may shed light on its function as a transcriptional regulator.

Results

To find additional FLASH-associated proteins, we performed a yeast two-hybrid (Y2H) screening with FLASH as bait and identified the SUMO E3 ligase PIAS1 as an interaction partner. The association appears to involve two distinct interaction surfaces in FLASH. We verified the interaction by Y2H-mating, GST pulldowns, co-IP and ChIP. FLASH and PIAS1 were found to co-localize in nuclear speckles. Functional assays revealed that PIAS1 enhances the intrinsic transcriptional activity of FLASH in a RING finger-dependent manner. Furthermore, PIAS1 also augments the specific activity of c-Myb, and cooperates with FLASH to further co-activate c-Myb. The three proteins, FLASH, PIAS1, and c-Myb, are all co-localized with active RNA polymerase II foci, resembling transcription factories.

Conclusions

We conclude that PIAS1 is a common partner for two cancer-related nuclear factors, c-Myb and FLASH. Our results point to a functional cooperation between FLASH and PIAS1 in the enhancement of c-Myb activity in active nuclear foci.
Appendix
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Metadata
Title
PIAS1 interacts with FLASH and enhances its co-activation of c-Myb
Authors
Anne Hege Alm-Kristiansen
Petra I Lorenzo
Ann-Kristin Molværsmyr
Vilborg Matre
Marit Ledsaak
Thomas Sæther
Odd S Gabrielsen
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2011
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-10-21

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