IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A novel role for the SR protein SF2/ASF as a regulator of SUMO conjugation
Autor/es:
FEDERICO PELISCH; ANABELLA SREBROW
Lugar:
Portugal
Reunión:
Conferencia; EURASNET (European Alternative Splicing Network) Annual Reporting Meeting; 2010
Institución organizadora:
EURASNET
Resumen:
Protein modification by conjugation of small ubiquitin-related modifiers (SUMO1, 2 and
3) is involved in diverse biological functions, namely transcription regulation, sub-cellular
partitioning, stress response, DNA damage repair and chromatin remodeling. SUMO
conjugation to target proteins proceeds by an enzymatic cascade involving an E1
activating enzyme, an E2 conjugating enzyme and several E3 ligases Since its discovery
more than a decade ago, there has been an enormous advance in the knowledge of many
aspects of the sumoylation pathway. However, there is a great void regarding its
components, mechanisms and consequences.
We found that the SR protein SF2/ASF is a regulator of the sumoylation pathway. Its
overexpression stimulates while its knockdown inhibits SUMO conjugation. SF2/ASF
interacts with the SUMO E2 enzyme Ubc9 and enhances sumoylation of specific
substrates, displaying a SUMO E3 ligase-like activity. In addition, SF2/ASF interacts with
the SUMO E3 ligase PIAS1, regulating PIAS1-induced overall protein sumoylation.
Interestingly, the RNA recognition motif 2 of SF2/ASF is necessary and sufficient for
sumoylation enhancement.
The influence of other SR proteins such as SRp20, SRp40 and SRp30c, on the SUMO
pathway was also studied. We found that the mere presence of any RRM2 is not sufficient
to confer the sumoylation-enhancing activity.
Moreover, SF2/ASF has a role in heat shock-induced sumoylation and promotes SUMO
conjugation to certain RNA processing factors.
These results add a new component to the sumoylation pathway and a new role for the
multi-functional SR protein SF2/ASF. It is possible to speculate that SF2/ASF could
function as a molecular link between sumoylation and RNA processing machineries.
Finding additional targets for SF2/ASF sumoylation-regulatory activity and deepening
into its physiological relevance is our immediate future challenge.