Diadenosines as FHIT-ness instructors.
FHIT is a tumor suppressor gene that is frequently inactivated in human cancer. Although the Fhit protein is known to hydrolyze diadenosine triphosphate (Ap(3)A), this hydrolase activity is not required for Fhit-mediated oncosuppression. Indeed, the molecular mechanisms and the regulatory elements of Fhit oncosuppression are largely unknown. Here, we review physiological and pathological aspects of Fhit in the context of the Ap(n)A family of signaling molecules, as well as the involvement of Fhit in apoptosis and the cell cycle in cancer models. We also discuss recent findings of novel Fhit interactions that may lead to new hypotheses about biochemical mechanisms underlying the oncosuppressor activity of this gene.
Department of Experimental Oncology, Molecular Biology Unit, Istituto Nazionale Tumori, Milan, Italy. manuela.campiglio@istitutotumori.mi.it
Manuela
M
Campiglio
Francesca
F
Bianchi
Francesca
F
Andriani
Gabriella
G
Sozzi
Elda
E
Tagliabue
Sylvie
S
Ménard
Luca
L
Roz
D000818:Animals; D015226:Dinucleoside Phosphates / Q000037:antagonists & inhibitors* / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; C011440:diadenosine triphosphate