TNF-related apoptosis-inducing ligand: signalling of a 'smart' molecule.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor super-family and signals via two death receptors, TRAIL-R1 and TRAIL-R2, and two decoy receptors, TRAIL-R3 and TRAIL-R4, differently expressed in normal and cancer cells. TRAIL is mainly studied for its capacity to induce apoptosis preferentially in cancer cells. TRAIL is expressed in a variety of human tissues, in particular in the lymphoid system, suggesting a strong physiological role in the innate immunity. This review will focus on TRAIL gene structure and regulation, protein folding, tissue expression and molecular signalling. Finally, the potential use of TRAIL as anticancer treatment alone or in combination therapy as well as the use of drugs which signal via TRAIL and its receptors will be analyzed.
Manzo
Fabio
F
Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Italy.
Nebbioso
Angela
A
Miceli
Marco
M
Conte
Mariarosaria
M
De Bellis
Floriana
F
Carafa
Vincenzo
V
Franci
Gianluigi
G
Tambaro
Francesco P
FP
Altucci
Lucia
L
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D017209:Apoptosis; D002986:Clinical Trials as Topic; D003601:Cytotoxicity Tests, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology* / Q000627:therapeutic use; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000970:Antineoplastic Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand