FHIT Human

The FHIT protein is characterized by a histidine triad motif (H-Φ-H-Φ-H-Φ-Φ, where Φ represents a hydrophobic amino acid) and belongs to the superfamily of nucleotide hydrolases and transferases . The enzyme typically forms a homodimer of ~15 kDa polypeptides, creating a ~30 kDa domain with a catalytic site . The hydrolytic activity of FHIT is Mg²⁺ dependent and follows a two-step mechanism .

FHIT is recognized as a tumor suppressor gene. Alterations and deletions in the FHIT gene are highly associated with the development of various human tumors, including those of the lung, cervix, breast, colon, stomach, and pancreas . Loss of heterozygosity (LOH), homozygous deletions, and abnormal expression of the FHIT gene have been implicated in several types of human malignancies .

Interestingly, the tumor suppressive function of FHIT is not solely dependent on its hydrolytic activity. Substrate binding or interaction with other proteins is also crucial for its role in tumor suppression . Overexpression of the wild-type FHIT gene has been shown to inhibit tumor cell growth, and direct injection of FHIT has significantly suppressed tumor growth in experimental models .

FHIT is involved in various biological processes, including the regulation of transcription, DNA-templated processes, and the intrinsic apoptotic signaling pathway mediated by p53 . It also plays a role in the negative regulation of proteasomal ubiquitin-dependent protein catabolic processes and purine nucleotide metabolic processes .