INVESTIGADORES
GIRARDINI BROVELLI Javier Enrique
congresos y reuniones científicas
Título:
THE PROLYL-ISOMERASE PIN1 REGULATES THE TIMING OF p53 ACTIVATION.
Autor/es:
MANTOVANI F.; GIRARDINI J.E.; TOCCO F.; BISSO A.; DEL SAL G.
Lugar:
New York
Reunión:
Simposio; 13th International p53 Workshop; 2006
Resumen:
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Phosphorylation-directed prolyl isomerization is emerging as
an important mechanism for fine-tuning of complex signaling networks. This is
based on the activity of the prolyl isomerase Pin1, which recognizes and
isomerizes phosphorylated Ser/Thr-Pro motifs on target proteins, thereby
modulating their functions. Pin1 has been implicated in the regulation of major
cellular events, such as cell cycle progression, transcription and apoptosis.
We, and others, have previously shown that Pin1 regulates the checkpoint
functions of p53.
p53 contains six Pin1-consensus sites at Ser33, Ser46,
Thr81, Ser127, Thr150 and Ser315. We have performed experiments aimed at better
characterizing the role of these phosphorylation events in regulating p53
functions, particularly apoptotic activity, as well as examining how Pin1
becomes involved in these processes both in normal cells under different stress
conditions as well as in tumor cells. We have constructed a panel of p53
phosphorylation mutants at Pin1 target sites, and generated inducible cell
lines expressing these proteins at physiological levels. We will present evidences that Pin1 regulates
the timing of p53 activation upon phosphorylation events triggered by diverse
stimuli, by rendering it suitable for subsequent modifications, in particular
acetylation of C-terminal residues by p300, and modulating its interaction with
target promoters and cofactors, among them members of the ASPP family.
