title: Hit proteins, mitochondria and cancer.
abstract: The histidine triad (HIT) superfamily comprises proteins that share the histidine triad motif, His-ϕ-His-ϕ-His-ϕ-ϕ, where ϕ is a hydrophobic amino acid. HIT proteins are ubiquitous in prokaryotes and eukaryotes. HIT proteins bind nucleotides and exert dinucleotidyl hydrolase, nucleotidylyl transferase or phosphoramidate hydrolase enzymatic activity. In humans, 5 families of HIT proteins are recognized. The accumulated epidemiological and experimental evidence indicates that two branches of the superfamily, the HINT (Histidine Triad Nucleotide Binding) members and FHIT (Fragile Histidine Triad), have tumor suppressor properties but a conclusive physiological role can still not be assigned to these proteins. Aprataxin forms another discrete branch of the HIT superfamily, is implicated in DNA repair mechanisms and unlike the HINT and FHIT members, a defective protein can be conclusively linked to a disease, ataxia with oculomotor apraxia type 1. The scavenger mRNA decapping enzyme, DcpS, forms a fourth branch of the HIT superfamily. Finally, the GalT enzymes, which exert specific nucleoside monophosphate transferase activity, form a fifth branch that is not implicated in tumorigenesis. The molecular mechanisms by which the HINT and FHIT proteins participate in bioenergetics of cancer are just beginning to be unraveled. Their purported actions as tumor suppressors are highlighted in this review.
authors.affiliation: Institute of Clinical Pharmacology and Visceral Research, University of Bern, Switzerland.
authors.forename: Juliette
authors.initials: J
authors.lastname: Martin
authors.forename: Marie V
authors.initials: MV
authors.lastname: St-Pierre
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dufour
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000502:physiology; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C097552:histidine triad protein; D006867:Hydrolases