Institute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, Germany.
System Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr. 11a, 07745 Jena, Germany.
Cells. 2023 Jan 17;12(3):353. doi: 10.3390/cells12030353.
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 and 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 . 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.
在之前的研究中，我们已经确定肿瘤抑制蛋白 Fhit（脆性组氨酸三联体）和 Nit1（腈水解酶 1）是β-catenin 的相互作用伙伴，它们都作为经典 Wnt 途径的抑制剂。有趣的是，在和中，这些蛋白质被表达为 NitFhit 融合蛋白。根据罗塞塔石假说，如果蛋白质在一个生物体中被表达为融合蛋白，而在其他生物体中被表达为单个蛋白，那么后者应该在物理上相互作用并表现出共同的信号功能。在这里，我们检验了这一假说，并提供了 Nit1 和 Fhit 之间直接关联的第一个生化证据。此外，纯化的重组人 Nit1 的分子筛层析显示出四聚体结构，这也与之前在 Rosetta Stone 融合蛋白 Nft-1 中观察到的结果一致。最后，与罗塞塔石假说一致，我们鉴定出 Hsp60 和 Ubc9 是 Nit1 和 Fhit 的其他共同相互作用伙伴。Nit1 和 Fhit 的相互作用可能会影响它们的酶活性以及与其他结合伙伴的相互作用。
