INVESTIGADORES
COLMAN LERNER Alejandro Ariel
congresos y reuniones científicas
Título:
REGULATION OF Akt ACTIVITY BY SUMO CONJUGATION
Autor/es:
GUILLERMO RISSO; FEDERICO PELISCH; BERTA POZZI; MATIAS BLAUSTEIN; ALEJANDRO COLMAN LERNER; ANABELLA SREBROW
Lugar:
Puerto Madryn - Chubut
Reunión:
Congreso; SAIB 46th Annual Meeting Argentine Society for Biochemistry and Molecular Biology XLVI Reunión Anual Sociedad Argentina en Bioquímica y Biología Molecular.; 2010
Institución organizadora:
Society for Biochemistry and Molecular Biology XLVI Reunión Anual Sociedad Argentina en Bioquímica y Biología Molecular.
Resumen:
A cell generates complex responses upon a variety of stimuli that it
receives within a multicellular organism. Our lab studies the
molecular mechanisms by which different extracellular cues
activate signaling pathways that control splicing factor activity at
different steps of gene expression regulation. Based on our previous
results demonstrating that: i) Pi3K/Akt pathway regulates
alternative splicing; ii) Akt phosphorylates SR proteins, in
particular SF2/ASF; and iii) SF2/ASF regulates SUMOylation, we
proposed to explore a possible regulatory feedback loop among the
components of the Pi3K/Akt/SR protein axis.We found that Akt1
and 2 are SUMOylation targets, as demonstrated by purification of
SUMOylated proteins from His-SUMO overexpressing cells by
Ni2+ affinity chromatography. We evaluated the effect of overexpressing
different SUMO E3 ligases on Akt SUMOylation.
Interestingly, SF2/ASF is capable of regulating Akt SUMOylation
and phosphorylation levels. We are further dissecting the
mechanism of Akt SUMOylation, its cross-talk with other Akt posttranslational
modifications, as well as the consequences on this
kinase activity. Akt pathways are involved in many cellular
functions and their dis-regulation associates with cancer, thus the
understanding of Akt activity regulation is not only relevant for cell
biology but may also help designing antitumoral therapeutic
strategies.2+ affinity chromatography. We evaluated the effect of overexpressing
different SUMO E3 ligases on Akt SUMOylation.
Interestingly, SF2/ASF is capable of regulating Akt SUMOylation
and phosphorylation levels. We are further dissecting the
mechanism of Akt SUMOylation, its cross-talk with other Akt posttranslational
modifications, as well as the consequences on this
kinase activity. Akt pathways are involved in many cellular
functions and their dis-regulation associates with cancer, thus the
understanding of Akt activity regulation is not only relevant for cell
biology but may also help designing antitumoral therapeutic
strategies.