[Todos] Seminarios conjuntos IFIBYNE-DFBMC- Jueves 9/8 - Dr. Bruno Amati

[Paula Felman]

>
>Seminario IFIBYNE-DFBMC Dr. Bruno Amati
>Jueves 9 de Agosto a las 13:00 horas.
>Italian Institute of Technology (IIT) & European 
>Institute of Oncology (IEO), Milan, Italy.
>
>Role of the prolyl-isomerase Pin1 in Myc-induced 
>lymphomagenesis: direct or indirect?
>The c-myc proto-oncogene is activated by 
>translocation in Burkitt's lymphoma and is 
>frequently subject to secondary mutations. 
>Substitutions in codon 58, in particular, 
>stabilize the c-Myc protein (Myc) and augment 
>its oncogenic potential. In wild-type Myc, 
>phosphorylation of Ser 62 primes phosphorylation 
>of Thr 58, providing a landing pad for the 
>peptidyl prolyl-isomerase Pin1, which in turn 
>promotes Ser 62 dephosphorylation and Myc 
>degradation. However, genetic data are missing 
>to address whether Pin1 influences Myc-induced 
>lymphomagenesis. We show here that genetic 
>ablation of Pin1 in Eµ-myc transgenic mice 
>starkly reduced lymphoma onset and penetrance. 
>In pre-malignant Pin1-deficient B-cells, the 
>proliferative response to Myc was selectively 
>impaired, in the absence of changes in either 
>steady-state Myc levels or Ser 62 
>phosphorylation. Similarly, in Pin1-/- mouse 
>embryo fibroblasts (MEFs), prolonged Myc 
>activation inhibited proliferation. In either 
>B-cells or MEFs, Myc-induced apoptosis occurred 
>independently from Pin1. Although Eµ-myc Pin1-/- 
>B-cells showed reduced activation of Myc-induced 
>mRNAs relative to Eµ-myc Pin1+/+ cells, 
>experiments in MEFs demonstrated that the 
>overall transcriptional activity of Myc was 
>independent from Pin1. Furthermore, upon 
>ablation of p53, Myc-induced lymphomas 
>progressed with or without Pin1, and with an 
>equally fast course. Thus, while Pin1 is not 
>essential for normal cell growth and mouse 
>development, it is required to support the 
>oncogenic activity of Myc in B-cells, most 
>likely via the selective suppression of a 
>p53-dependent growth-inhibitory checkpoint.
>
>Host: ARK
>
>--
>Francisco J. Urbano, PhD.
>IFIBYNE-CONICET
>Intendente Güiraldes 2160
>Facultad Ciencias Exactas
>Pabellon 2- Piso 2
>Ciudad Universitaria
>(C1428EGA) Buenos Aires
>ARGENTINA
>Email: <mailto:fjurbano en fbmc.fcen.uba.ar>fjurbano en fbmc.fcen.uba.ar,
><mailto:fran.j.urbano en gmail.com>fran.j.urbano en gmail.com
>Phone: (+54)-11-4576 3368
>Fax: (+54)-11-4576 3321
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