Fragile histidine triad protein (FHIT)

Fragile histidine triad protein (FHIT) is an enzyme and tumor suppressor encoded by the FHIT gene on human chromosome 3p14.2, a region frequently deleted or altered in cancer[1][3]. FHIT is a member of the histidine triad (HIT) family of nucleotide hydrolases and transferases, characterized structurally by a conserved histidine triad motif and known for Mg²⁺-dependent hydrolysis of diadenosine polyphosphates, particularly Ap₃A, yielding ADP and AMP[1][2][3][4]. The protein functions in purine metabolism, and loss of FHIT due to gene deletion, loss of heterozygosity, or decreased expression is associated with carcinogenesis in multiple tumor types; its tumor suppressor activity is linked to induction of apoptosis, with evidence suggesting this is mediated by the FHIT-substrate complex rather than hydrolase activity alone[1][4][5][6]. There are no approved drugs directly targeting FHIT, but its loss is a recognized biomarker in cancer diagnosis and prognosis[1][3][6].

Other names

FHITBis(5'-adenosyl)-triphosphataseAP3AaseFRA3Bfragile histidine triadfragile histidine triad diadenosine triphosphatasetríada histidina fràgil

FHIT acts as a tumor suppressor primarily via proapoptotic signaling, possibly by binding and/or hydrolyzing diadenosine polyphosphates; mutation or loss leads to reduced apoptotic activity and increased cancer risk FHIT-substrate complex formation is believed to send the tumor suppression (apoptosis) signal, independent of its hydrolase activity