Department of Sciences and Chemical Technologies, University of Rome Tor Vergata, Rome, Italy.
Biochemistry. 2010 Jan 19;49(2):252-8. doi: 10.1021/bi9012676.
RTN1-C protein is a membrane protein localized in the ER and expressed in the nervous system, and its biological role is not completely clarified. Our previous studies have shown that the C-terminal region of RTN1-C, corresponding to the fragment from residues 186 to 208, was able to bind the nucleic acids and to interact with histone deacetylase (HDAC) enzymes. In the present work the properties of the synthetic RTN1-C(CT) peptide corresponding to this region were studied with relation to its ability to bind the metal ions in its N-terminal region. RTN1-C(CT) peptide is characterized by the presence of high-affinity copper and nickel ion sites. The nuclease activity of the metal-peptide complex was observed due to the presence of an ATCUN-binding motif. Moreover, the effect of the Cu/Ni-RTN1-C(CT) complexes on the HDAC activity was investigated. The histone deacetylase inhibitors are a new class of antineoplastic agents currently being evaluated in clinical trials. Our data show that the acetylated form of the metal-peptide complex is able to inhibit the HDAC activity at micromolar concentrations. These results allow to propose the Cu/Ni-RTN1-C(CT) complexes as models for the design of antitumor agents.
RTN1-C 蛋白是一种定位于内质网的膜蛋白，在神经系统中表达，其生物学功能尚不完全清楚。我们以前的研究表明，RTN1-C 的 C 端区域（对应于残基 186 到 208 的片段）能够结合核酸并与组蛋白去乙酰化酶（HDAC）酶相互作用。在本工作中，研究了与该区域对应的合成 RTN1-C(CT)肽的性质与其在其 N 端区域结合金属离子的能力有关。RTN1-C(CT)肽的特征是存在高亲和力的铜和镍离子结合位点。由于存在 ATCUN 结合基序，观察到了金属-肽复合物的核酸酶活性。此外，还研究了 Cu/Ni-RTN1-C(CT) 复合物对 HDAC 活性的影响。组蛋白去乙酰化酶抑制剂是目前正在临床试验中评估的一类新型抗肿瘤药物。我们的数据表明，金属-肽复合物的乙酰化形式能够以微摩尔浓度抑制 HDAC 活性。这些结果允许将 Cu/Ni-RTN1-C(CT) 复合物作为设计抗肿瘤剂的模型。
