FHIT

{{Short description|Protein-coding gene in the species Homo sapiens}}

Bis(5'-adenosyl)-triphosphatase also known as fragile histidine triad protein (FHIT) is an enzyme that in humans is encoded by the FHIT gene.{{cite journal | vauthors = Ohta MH, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Croce CM, Huebner K | title = The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers | journal = Cell | volume = 84 | issue = 4 | pages = 587–97 | date = Apr 1996 | pmid = 8598045 | doi = 10.1016/S0092-8674(00)81034-X | s2cid = 18792069 | doi-access = free }}{{cite journal | vauthors = Pekarsky Y, Campiglio M, Siprashvili Z, Druck T, Sedkov Y, Tillib S, Draganescu A, Wermuth P, Rothman JH, Huebner K, Buchberg AM, Mazo A, Brenner C, Croce CM | title = Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 15 | pages = 8744–9 | date = Aug 1998 | pmid = 9671749 | pmc = 21147 | doi = 10.1073/pnas.95.15.8744 | bibcode = 1998PNAS...95.8744P | doi-access = free }}

Function

FHIT is also known as human accelerated region 10. It may, therefore, have played a key role in differentiating humans from apes.{{cite journal | vauthors = Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D | title = An RNA gene expressed during cortical development evolved rapidly in humans | journal = Nature | volume = 443 | issue = 7108 | pages = 167–72 | date = 2006-08-16 | pmid = 16915236 | doi = 10.1038/nature05113 | bibcode = 2006Natur.443..167P | s2cid = 18107797 | url = https://dipot.ulb.ac.be/dspace/bitstream/2013/51805/3/pollard2006.pdf }} [http://www.nature.com/nature/journal/v443/n7108/extref/nature05113-s1.doc supplement]

This gene, a member of the histidine triad gene family, encodes a diadenosine

P1,P3-bis(5'-adenosyl)-triphosphate adenylohydrolase involved in purine metabolism. The gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts of this gene. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas.{{cite web | title = Entrez Gene: FHIT fragile histidine triad gene| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2272}}

Though the exact molecular function of FHIT is still partially unclear, the gene works as a tumor suppressor as it has been demonstrated in animal studies.{{cite journal | vauthors = Fong LY, Fidanza V, Zanesi N, Lock LF, Siracusa LD, Mancini R, Siprashvili Z, Ottey M, Martin SE, Druck T, McCue PA, Croce CM, Huebner K | title = Muir-Torre-like syndrome in Fhit-deficient mice | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 9 | pages = 4742–7 | date = April 2000 | pmid = 10758156 | pmc = 18303 | doi = 10.1073/pnas.080063497 | bibcode = 2000PNAS...97.4742F | doi-access = free }}{{cite journal | vauthors = Zanesi N, Fidanza V, Fong LY, Mancini R, Druck T, Valtieri M, Rüdiger T, McCue PA, Croce CM, Huebner K | title = The tumor spectrum in FHIT-deficient mice | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 18 | pages = 10250–5 | date = August 2001 | pmid = 11517343 | pmc = 56947 | doi = 10.1073/pnas.191345898 | bibcode = 2001PNAS...9810250Z | doi-access = free }}{{cite journal | vauthors = Zanesi N, Pekarsky Y, Croce CM | title = A mouse model of the fragile gene FHIT: From carcinogenesis to gene therapy and cancer prevention | journal = Mutat. Res. | volume = 591 | issue = 1–2 | pages = 103–9 | date = December 2005 | pmid = 16085127 | doi = 10.1016/j.mrfmmm.2005.05.016 }} Furthermore FHIT has been shown to synergize with VHL, another tumor suppressor, in protecting against chemically - induced lung cancer.{{cite journal | vauthors = Zanesi N, Mancini R, Sevignani C, Vecchione A, Kaou M, Valtieri M, Calin GA, Pekarsky Y, Gnarra JR, Croce CM, Huebner K | title = Lung cancer susceptibility in Fhit-deficient mice is increased by Vhl haploinsufficiency | journal = Cancer Res. | volume = 65 | issue = 15 | pages = 6576–82 | date = August 2005 | pmid = 16061637 | doi = 10.1158/0008-5472.CAN-05-1128 | doi-access = }}

FHIT also acts as a tumor suppressor of HER2/neu driven breast cancer.{{cite journal | vauthors = Bianchi F, Tagliabue E, Ménard S, Campiglio M | title = Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections | journal = Cell Cycle | volume = 6 | issue = 6 | pages = 643–6 | date = March 2007 | pmid = 17374991 | doi = 10.4161/cc.6.6.4033 | doi-access = free | hdl = 2434/810034 | hdl-access = free }}

Interactions

FHIT has been shown to interact with UBE2I.{{cite journal | vauthors = Shi Y, Zou M, Farid NR, Paterson MC | title = Association of FHIT (fragile histidine triad), a candidate tumour suppressor gene, with the ubiquitin-conjugating enzyme hUBC9 | journal = Biochem. J. | volume = 352 Pt 2 | issue = 2 | pages = 443–8 | date = December 2000 | pmid = 11085938 | pmc = 1221476 | doi = 10.1042/0264-6021:3520443 }}

References

External links

{{PDBe-KB2|P49789|Bis(5'-adenosyl)-triphosphatase}}