Beta-catenin takes a HIT.
Histidine triad (HIT) proteins represent a small family of nucleotide-binding and -hydrolyzing proteins, which attracted the attention of cancer biologists because their expression is lost in multiple human malignancies. To some of the family members including Fhit, Hint1 and Hint2, a tumor suppressive activity was assigned. Although highly similar in structure, their mode of action appears to be different as they are not able to compensate each other's function. Surprisingly, in any reported assay system the enzymatic activity of the histidine triad proteins was not required for their tumor suppressor function. Until recently, little was known about the molecular mechanisms mediating the tumor suppressor activities of histidine triad proteins. The identification of new interaction partners started to shed light on the signaling pathways modulated by the HIT proteins. Here, we summarize these findings with special emphasis on the histidine triad proteins Hint1 and Fhit and their repressive activity on the beta-catenin signaling function.
Huber
Otmar
O
Department of Laboratory Medicine and Pathobiochemistry, Campus Benjamin Franklyn, Charité-Universitätsmedizin Berlin, Berlin, Germany. otmar.huber@charite.de
Weiske
Jörg
J
D017766:Acid Anhydride Hydrolases / Q000502:physiology*; D000818:Animals; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011485:Protein Binding; D015398:Signal Transduction; D051176:beta Catenin / Q000502:physiology*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051176:beta Catenin; D000099170:Bis(5'-adenosyl)triphosphatase; C063306:HINT1 protein, human; C489275:Hint1 protein, mouse