含犰狳重复蛋白 (ARMC) 是在真核生物中发现的一个大家族，在细胞粘附、信号传导和细胞骨架调节中发挥着重要作用。 ARMC6 蛋白在包括人类在内的灵长类动物中高度保守，但迄今为止，除了最初暗示与癌症和端粒酶活性有关之外，还没有明确的功能。我们在这里报告的体外实验显示 ARMC6 与来自几个癌症相关基因（例如 EGFR、VEGF 和 c-MYC）的 DNA 启动子序列以及端粒 RNA 重复序列 (TERRA) 结合。 ARMC6 结合活性似乎可以识别 G-四链体基序，这些基序越来越多地被认为是染色体维护和修复中基于结构的蛋白质结合位点。 ARMC6 功能的体内研究表明，当该蛋白在人类细胞系中过表达时，与致癌途径相关的基因和与下游非规范端粒酶途径相关的基因（例如 VEGF、hTERT、c-MYC、ESM1）会出现不同的表达。 ，MMP3）。已知 ARMC6 会与人类庇护蛋白 TRF2 和端粒酶相互作用。该蛋白与 G 四链体结构结合，并且优先与 RNA 结合而不是与 DNA 结合。因此，该蛋白质可能是非规范核酸结构基序如何在基因调控和端粒染色质重排途径之间进行介导的一个例子。版权所有 © 2024。由 Elsevier B.V. 出版。

Armadillo repeat-containing proteins (ARMCs) are a large family found throughout eukaryotes, which play prominent roles in cell adhesion, signaling and cytoskeletal regulation. The ARMC6 protein is highly conserved in primates, including humans, but to date does not have a clear function beyond initial hints of a link to cancer and telomerase activity. We report here in vitro experiments showing ARMC6 binding to DNA promoter sequences from several cancer-related genes (e.g., EGFR, VEGF and c-MYC), and also to the telomeric RNA repeat (TERRA). ARMC6 binding activity appears to recognize G-quadruplex motifs, which are being increasingly implicated as structure-based protein binding sites in chromosome maintenance and repair. In vivo investigation of ARMC6 function revealed that when this protein is overexpressed in human cell lines, there is different expression of genes connected with oncogenic pathways and those implicated in downstream non-canonical telomerase pathways (e.g., VEGF, hTERT, c-MYC, ESM1, MMP3). ARMC6 is already known to interact with human shelterin protein TRF2 and telomerase. The protein binds G-quadruplex structures and does so preferentially to RNA over DNA. As such, this protein may be an example of how a non-canonical nucleic acid structural motif allows mediation between gene regulation and telomeric chromatin rearrangement pathways.Copyright © 2024. Published by Elsevier B.V.