ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells. (Articolo in rivista) (literal)

Anno

• 2008-01-01T00:00:00+01:00 (literal)

Alternative label

• Stagni V, di Bari MG, Cursi S, Condò I, Cencioni MT, Testi R, Lerenthal Y, Cundari E, Barilà D. (2008)
  ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells.
  in Blood
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Stagni V, di Bari MG, Cursi S, Condò I, Cencioni MT, Testi R, Lerenthal Y, Cundari E, Barilà D. (literal)

Pagina inizio

• 829 (literal)

Pagina fine

• 837 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 111 (literal)

Rivista

• Blood (Rivista)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Dulbecco Telethon Institute, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy. (literal)

Titolo

• ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells. (literal)

Abstract

• Ataxia telangiectasia (A-T) is a rare cancer-predisposing genetic disease, caused by the lack of functional ATM kinase, a major actor of the double strand brakes (DSB) DNA-damage response. A-T patients show a broad and diverse phenotype, which includes an increased rate of lymphoma and leukemia development. Fas-induced apoptosis plays a fundamental role in the homeostasis of the immune system and its defects have been associated with autoimmunity and lymphoma development. We therefore investigated the role of ATM kinase in Fas-induced apoptosis. Using A-T lymphoid cells, we could show that ATM deficiency causes resistance to Fas-induced apoptosis. A-T cells up-regulate FLIP protein levels, a well-known inhibitor of Fas-induced apoptosis. Reconstitution of ATM kinase activity was sufficient to decrease FLIP levels and to restore Fas sensitivity. Conversely, genetic and pharmacologic ATM kinase inactivation resulted in FLIP protein up-regulation and Fas resistance. Both ATM and FLIP are aberrantly regulated in Hodgkin lymphoma. Importantly, we found that reconstitution of ATM kinase activity decreases FLIP protein levels and restores Fas sensitivity in Hodgkin lymphoma-derived cells. Overall, these data identify a novel molecular mechanism through which ATM kinase may regulate the immune system homeostasis and impair lymphoma development. (literal)

Prodotto di

• Institute of molecular biology and pathology (IBPM) (Istituto)
• Meccanismi molecolari del ciclo cellulare e della mitosi (SV.P15.011.001) (Modulo)

Autore CNR

• ENRICO CUNDARI (Persona)

Incoming links:

Prodotto

• Institute of molecular biology and pathology (IBPM) (Istituto)
• Meccanismi molecolari del ciclo cellulare e della mitosi (SV.P15.011.001) (Modulo)

Autore CNR di

• ENRICO CUNDARI (Persona)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Blood (Rivista)