Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
Instituto de Tecnologías Biomédicas, Centro de Investigaciones Biomédicas de Canarias, Facultad de Medicina, Campus Ciencias de la Salud, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
Expert Rev Mol Med. 2024 Sep 25;26:e19. doi: 10.1017/erm.2024.10.
ATXN3 is a ubiquitin hydrolase (or deubiquitinase, DUB), product of the gene, ubiquitously expressed in various cell types including peripheral and neuronal tissues and involved in several cellular pathways. Importantly, the expansion of the CAG trinucleotides within the gene leads to an expanded polyglutamine domain in the encoded protein, which has been associated with the onset of the spinocerebellar ataxia type 3, also known as Machado-Joseph disease, the most common dominantly inherited ataxia worldwide. ATXN3 has therefore been under intensive investigation for decades. In this review, we summarize the main functions of ATXN3 in proteostasis, DNA repair and transcriptional regulation, as well as the emerging role in regulating chromatin structure. The mentioned molecular functions of ATXN3 are also reviewed in the context of the pathological expanded form of ATXN3.
ATXN3 是一种泛素水解酶（或去泛素化酶，DUB），由 基因编码，在包括外周和神经元组织在内的各种细胞类型中广泛表达，参与多种细胞途径。重要的是， 基因内 CAG 三核苷酸的扩展导致编码蛋白中多谷氨酰胺结构域的扩展，这与脊髓小脑共济失调 3 型（也称为 Machado-Joseph 病）的发病有关，这是全球最常见的显性遗传性共济失调。因此，ATXN3 数十年来一直受到深入研究。在这篇综述中，我们总结了 ATXN3 在蛋白质平衡、DNA 修复和转录调控中的主要功能，以及在调节染色质结构方面的新兴作用。还在病理扩展形式的 ATXN3 背景下综述了 ATXN3 的所述分子功能。
