FHIT
Description
The FHIT (fragile histidine triad diadenosine triphosphatase) is a protein-coding gene located on chromosome 3.
FHIT, also known as fragile histidine triad protein, is an enzyme encoded by the FHIT gene. It is involved in purine metabolism and has been identified as a tumor suppressor. FHIT is a member of the histidine triad gene family and its gene encompasses the fragile site FRA3B on chromosome 3. This fragile site is prone to damage by carcinogens, which can lead to translocations and aberrant transcripts of the FHIT gene. Aberrant transcripts have been found in a significant proportion of esophageal, stomach, and colon carcinomas. The exact function of FHIT is still under investigation, but its role as a tumor suppressor has been demonstrated in animal studies. FHIT synergizes with VHL, another tumor suppressor, to protect against chemically-induced lung cancer. It also acts as a tumor suppressor in HER2/neu-driven breast cancer. Furthermore, FHIT may have played a key role in human evolution, as it is also known as human accelerated region 10, suggesting its importance in differentiating humans from apes.
FHIT, also known as fragile histidine triad protein, is an enzyme involved in purine metabolism. It exhibits dinucleoside triphosphate hydrolase activity, cleaving P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. It can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A) but has low activity with ATP. Additionally, FHIT exhibits adenylylsulfatase, adenosine 5'-monophosphoramidase, and adenylylsulfate-ammonia adenylyltransferase activities. It modulates transcriptional activation by CTNNB1, regulates the expression of genes essential for cell proliferation and survival, and plays a role in apoptosis induction via SRC and AKT1 signaling pathways. FHIT inhibits MDM2-mediated proteasomal degradation of p53/TP53, contributing to p53/TP53-mediated apoptosis. Its apoptosis-inducing function depends on binding to P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds but does not require catalytic activity. A mitochondrial form of FHIT enhances mitochondrial calcium uptake. FHIT acts as a tumor suppressor. It forms homodimers and interacts with UBE2I, MDM2, and CTNNB1. It has been identified in a complex with CTNNB1 and LEF1.
FHIT is also known as AP3Aase, FRA3B.
