IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Involvement of SF2/ASF in the SUMOylation pathway: a novel role for SR proteins beyond alternative splicing
Autor/es:
FEDERICO PELISCH; ANABELLA SREBROW
Lugar:
Assisi, Italia
Reunión:
Congreso; EURASNET Annual Reporting Meeting; 2009
Institución organizadora:
European Alternative Splicing Network (EURASNET)
Resumen:
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Ser/Arg-rich (SR) proteins,
initially described as regulators of both constitutive and alternative
splicing, have been shown to play important roles in other steps of gene
expression such as transcription, mRNA export, mRNA stability, non-sense
mediated decay, translation and genome stability.
SUMO (small ubiquitin-related
modifier) is a reversible post-translational protein modifier with a
three-dimensional structure similar to that of ubiquitin. Like ubiquitination,
the SUMOylation pathway consists of a SUMO-specific enzymatic cascade involving
an E1 activating enzyme, an E2 conjugating enzyme, and SUMO E3 ligases, which
although not absolutely required for the process, facilitate the transfer of
SUMO from the conjugating enzyme to a SUMOylation substrate. Among E3 ligases,
PIAS proteins, RanBP2 and Pc2 have been characterized. Unlike ubiquitination,
SUMOylation does not target proteins for proteolytic breakdown, but regulates
protein function, nuclear targeting and the formation of sub-cellular
structures, mainly by altering protein-protein interactions.
Taking into account previous
reports indicating that the E3 ligase PIAS1 localizes to nuclear speckles,
resembles scaffold-attachment factors shown to interact with RNA pol II and SR
proteins, and is part of the human spliceosome, we decided to investigate a
possible involvement of SR proteins in the SUMOylation process.
We found that over-expression
of SF2/ASF strongly enhances SUMOylation in vivo. Surprisingly, knockdown of
SF2/ASF has a drastic inhibitory effect on global SUMOylation. Furthermore,
SF2/ASF interacts with the SUMO E3 ligase PIAS, both physically and
functionally. The stimulatory effect on SUMOylation is observed in different
cell lines, depends on the second RRM of SF2/ASF, and is not restricted to this
particular SR protein. These results show that certain SR proteins are critical
for the normal function of the SUMOylation pathway and enlarge the ever growing
list of cellular functions associated to this family of proteins, originally
known as only splicing regulators.