The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Caenorhabditis elegans*/metabolism ; Tumor Suppressor Proteins*; Animals ; Humans ; Acid Anhydride Hydrolases/metabolism ; Drosophila melanogaster/metabolism ; Hydrolases ; Recombinant Proteins

In previous studies, we have identified the tumor suppressor proteins Fhit (fragile histidine triad) and Nit1 (Nitrilase1) as interaction partners of β-catenin both acting as repressors of the canonical Wnt pathway. Interestingly, in D. melanogaster and C. elegans these proteins are expressed as NitFhit fusion proteins. According to the Rosetta Stone hypothesis, if proteins are expressed as fusion proteins in one organism and as single proteins in others, the latter should interact physically and show common signaling function. Here, we tested this hypothesis and provide the first biochemical evidence for a direct association between Nit1 and Fhit. In addition, size exclusion chromatography of purified recombinant human Nit1 showed a tetrameric structure as also previously observed for the NitFhit Rosetta Stone fusion protein Nft-1 in C. elegans . Finally, in line with the Rosetta Stone hypothesis we identified Hsp60 and Ubc9 as other common interaction partners of Nit1 and Fhit. The interaction of Nit1 and Fhit may affect their enzymatic activities as well as interaction with other binding partners.

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Keywords: Fhit; Hsp60; Nit1; NitFhit; Rosetta Stone hypothesis; Ubc9; tumor suppressor

EC 3.6.- (Acid Anhydride Hydrolases)
EC 3.- (Hydrolases)
0 (Recombinant Proteins)
0 (Tumor Suppressor Proteins)
0 (fragile histidine triad protein)

Date Created: 20230211 Date Completed: 20230227 Latest Revision: 20230227

20230227

PMC9913352

10.3390/cells12030353

36766695