The Fragile Histidine Triad (FHIT) protein is a member of the histidine triad gene family. The FHIT gene encodes a diadenosine 5’,5’‘’-P1,P3-triphosphate hydrolase, an enzyme involved in purine metabolism . This gene includes the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and abnormal transcripts of this gene .
The FHIT protein is expressed as a human recombinant protein with a Glutathione S-transferase (GST) tag. This recombinant protein is produced in Escherichia coli and shows a 43 kDa band on SDS-PAGE . The GST tag aids in the purification and detection of the protein. The FHIT protein is a single, non-glycosylated polypeptide chain containing 155 amino acids and has a molecular mass of 17.9 kDa .
The primary function of the FHIT protein is to act as a hydrolase that cleaves diadenosine triphosphate (Ap3A) to ADP and AMP . This enzyme-substrate complex is believed to be the tumor suppressor signal . The FHIT protein plays a crucial role in purine metabolism and is involved in the regulation of various cellular processes.
The FHIT gene is a tumor suppressor gene, and its expression is often reduced or lost in numerous types of cancer, including lung, cervix, breast, colon, stomach, and pancreas . Alterations and deletions of the FHIT gene are strongly linked to the genesis and establishment of these tumors . The restoration of FHIT expression in FHIT-deficient cancer cells leads to apoptosis, involving the intrinsic caspase pathway, in cancer-derived cells and in tumor xenografts .