Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR), 80131 Naples, Italy.
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
Int J Mol Sci. 2024 Aug 14;25(16):8863. doi: 10.3390/ijms25168863.
The "AT-hook" is a peculiar DNA-binding domain that interacts with DNA in the minor groove in correspondence to AT-rich sequences. This domain has been first described in the HMGA protein family of architectural factors and later in various transcription factors and chromatin proteins, often in association with major groove DNA-binding domains. In this review, using a literature search, we identified about one hundred AT-hook-containing proteins, mainly chromatin proteins and transcription factors. After considering the prototypes of AT-hook-containing proteins, the HMGA family, we review those that have been studied in more detail and that have been involved in various pathologies with a particular focus on cancer. This review shows that the AT-hook is a domain that gives proteins not only the ability to interact with DNA but also with RNA and proteins. This domain can have enzymatic activity and can influence the activity of the major groove DNA-binding domain and chromatin docking modules when present, and its activity can be modulated by post-translational modifications. Future research on the function of AT-hook-containing proteins will allow us to better decipher their function and contribution to the different pathologies and to eventually uncover their mutual influences.
“AT 钩”是一种特殊的 DNA 结合域，与富含 AT 的序列相对应，与 DNA 的小沟相互作用。该结构域最初在 HMGA 蛋白家族的结构因子中被描述，后来在各种转录因子和染色质蛋白中被发现，通常与大沟 DNA 结合域相关联。在这篇综述中，我们通过文献检索，确定了大约 100 种含有 AT 钩的蛋白质，主要是染色质蛋白和转录因子。在考虑了含有 AT 钩的蛋白质原型，即 HMGA 家族之后，我们回顾了那些被更详细研究并与各种病理学相关的蛋白质，特别是癌症。这篇综述表明，AT 钩是一种赋予蛋白质与 DNA 相互作用能力的结构域，也能与 RNA 和蛋白质相互作用。该结构域具有酶活性，可以影响大沟 DNA 结合域和染色质停泊模块的活性，其活性可以通过翻译后修饰来调节。对含有 AT 钩的蛋白质功能的进一步研究，将使我们能够更好地破译它们在不同病理学中的功能和作用，并最终揭示它们之间的相互影响。
