Skip to Main Content (Press Enter)

Logo UNITO
  • ×
  • Home
  • Pubblicazioni
  • Progetti
  • Persone
  • Competenze
  • Settori
  • Strutture
  • Terza Missione

UNI-FIND
Logo UNITO

|

UNI-FIND

unito.it
  • ×
  • Home
  • Pubblicazioni
  • Progetti
  • Persone
  • Competenze
  • Settori
  • Strutture
  • Terza Missione
  1. Pubblicazioni

The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL

Articolo
Data di Pubblicazione:
2009
Abstract:
Anaplastic large cell lymphoma (ALCL) represent a subset of neoplasms often caused by translocations that juxtapose the anaplastic lymphoma kinase (ALK) to a dimerization partner. The constitutive activation of ALK fusion proteins leads to cellular transformation through a complex signaling network. To further elucidate the ALK pathways sustaining lymphomagenesis and tumor maintenance, we analyzed the tyrosine-kinase protein profiles of ALK-positive cell lines using two complementary proteomic-based approaches, taking advantage of a specific ALK RNA interference (RNAi) or cell-permeable inhibitors. A well-defined set of ALK-associated tyrosine phospho-peptides, including metabolic enzymes, kinases, ribosomal and cytoskeletal proteins was identified. Validation studies confirmed that VASP and ATIC associated with NPM-ALK and their phosphorylation required ALK activity. ATIC phosphorylation was also documented in cell lines and primary tumors carrying ALK proteins and other tyrosine kinases, including TPR-Met and wild type c-Met. Functional analyses revealed that ALK-mediated ATIC phosphorylation enhanced its enzymatic activity, dampering the methotrexate-mediated transformylase activity inhibition. These findings demonstrate that alternative proteomic approaches in well-controlled experimental settings allow the definition of highly-informative proteomic profiles and the discovery of novel ALK-downstream players that contribute to the maintenance of the neoplastic phenotype. Prediction of tumor responses to methotrexate may justify the design of specific molecular-based chemotherapy.
Tipologia CRIS:
03A-Articolo su Rivista
Elenco autori:
Boccalatte FE; Voena C; Riganti C; Bosia A; D'Amico L; Riera L; Cheng M; Ruggeri B; Jensen ON; Goss VL; Lee K; Nardone J; Rush J; Polakiewicz RD; Comb MJ; Chiarle R; Inghirami G
Autori di Ateneo:
CHIARLE Roberto
RIGANTI Chiara
VOENA Claudia
Link alla scheda completa:
https://iris.unito.it/handle/2318/55041
Pubblicato in:
BLOOD
Journal
  • Dati Generali

Dati Generali

URL

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18845790
  • Utilizzo dei cookie

Realizzato con VIVO | Designed by Cineca | 25.6.1.0