Premium
ABIN1 inhibits HDAC1 ubiquitination and protects it from both proteasome‐ and lysozyme‐dependent degradation
Author(s) -
Ma Yuhong,
Yuan Sen,
Tian Xuezhang,
Lin Shanchuan,
Wei Shangmou,
Hu Tongtong,
Chen Shiyou,
Li Xueqing,
Chen Shuliang,
Wu Dongcheng,
Wang Min,
Guo Deyin
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26428
Subject(s) - regulator , microbiology and biotechnology , ubiquitin , proteasome , hdac1 , immune system , biology , suppressor , regulation of gene expression , cancer research , chemistry , gene , biochemistry , immunology , histone deacetylase , histone
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.