ABIN1, an important immune regulator, has been shown to be involved in various cellular functions, such as immunity, development, tissue homeostasis, and tumor progression. It inhibits TNF- and TLR-induced NF-κB signaling activation and the consequent gene expression. Despite its functional significance, the mechanism of ABIN1 in the regulation of various cellular functions remains unclear. In this study, we identified HDAC1, a key regulator of eukaryotic gene expression and many important cellular events, including cell proliferation, differentiation, cancer and immunity, as an interacting partner of ABIN1. The results showed that ABIN1 acted as a modulator to down-regulate HDAC1 ubiquitination via three different linkages, thereby stabilizing HDAC1 by inhibiting its lysosomal and proteasomal degradation. Interestingly, the inhibitory function of ABIN1 required direct binding with HDAC1. Moreover, the level of p53, which was a tumor suppressor and a well-studied substrate of HDAC1, was under the regulation of ABIN1 via the modulation of HDAC1 levels, suggesting that ABIN1 was physiologically significant in tumor progression. This study has revealed a new function of ABIN1 in mediating HDAC1 modification and stability.

中文翻译：

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ABIN1抑制HDAC1泛素化，并保护其免受蛋白酶体和溶菌酶依赖性降解。

ABIN1是一种重要的免疫调节剂，已被证明与多种细胞功能有关，例如免疫力，发育，组织稳态和肿瘤进展。它抑制TNF和TLR诱导的NF-κB信号传导激活以及随后的基因表达。尽管具有功能重要性，但尚不清楚ABIN1在调节各种细胞功能中的机制。在这项研究中，我们确定了HDAC1，它是真核基因表达和许多重要细胞事件（包括细胞增殖，分化，癌症和免疫）的关键调节剂，是ABIN1的相互作用伴侣。结果表明，ABIN1通过三个不同的连接作为下调HDAC1泛素化的调节剂，从而通过抑制其溶酶体和蛋白酶体降解来稳定HDAC1。有趣的是，ABIN1的抑制功能需要与HDAC1直接结合。此外，通过抑制HDAC1水平，作为肿瘤抑制因子和HDAC1研究底物的p53的水平受ABIN1的调节，表明ABIN1在肿瘤进展中具有重要的生理意义。这项研究揭示了ABIN1在介导HDAC1修饰和稳定性方面的新功能。