Fragile histidine triad diadenosine triphosphatase (FHIT)

Fragile histidine triad diadenosine triphosphatase (FHIT) is an enzyme encoded by the FHIT gene located at chromosome 3p14.2, a region frequently deleted or altered in various human cancers[3][2]. FHIT protein is a member of the HIT (histidine triad) family of nucleotide hydrolases, catalyzing the hydrolysis of dinucleoside 5’,5’’–P^1,P^3-triphosphates such as Ap3A to AMP and ADP[1][4]. Structurally, it forms a homodimer with a catalytic site containing conserved histidines critical for activity[1][2]. Unlike many kinases and phosphatases, FHIT functions as a tumor suppressor—loss or abnormal expression leads to promotion of tumorigenesis in various tissue types[3][4]. Biochemically, it has roles in signaling apoptosis, particularly via mitochondrial pathways and in response to DNA damage. FHIT loss is considered a biomarker of malignancy in several cancers, but there are currently no drugs directly targeting this enzyme for therapeutic purposes[3][7].

Other names

Fragile histidine triad proteinFHIT protein

For potential therapeutics, mechanisms would likely involve modulation of FHIT's enzymatic activity or its apoptosis-inducing function, but this remains largely theoretical, as no drugs are clinically approved or well-studied in this context[7][3].