fragile histidine triad protein; AP3A hydrolase; bis(5'-adenosyl)-triphosphatase; diadenosine 5',5'-P1,P3-triphosphate hydrolase (FHIT)

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Function

cleaves A-5'-PPP-5'A to yield AMP & ADP
modulates transcriptional activation by CTNNB1 thus role in expression of genes essential for cell proliferation & survival, such as CCND1 & BIRC5
role in the induction of apoptosis via SRC & AKT1 signaling
inhibits MDM2-mediated proteasomal degradation of p53/TP53 thus a role in p53/TP53-mediated apoptosis
induction of apoptosis may in part come from the mitochondrial form, which sensitizes the low-affinity Ca+2 transporters, enhancing mitochondrial Ca+2 uptake.
phosphorylation at Tyr-114 by SRC is required for induction of apoptosis
interacts with UBE2I, MDM2, CTNNB1
identified in a complex with CTNNB1 & LEF1
possible tumor suppressor for specific tissues

chromosomal translocation t(3;8)(p14.2;q24.1) involving FHIT & RNF139 has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma & thyroid carcinoma
- the 3p14.2 breakpoint interrupts FHIT in its 5' non-coding region, but it is unlikely that FHIT is causally related to renal cell carcinoma or thyroid carcinoma
associated with digestive tract cancers
- tumors are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B
- abnormal transcripts of FHIT found in ~50% of