TY - JOUR
T1 - ABIN1 inhibits HDAC1 ubiquitination and protects it from both proteasome- and lysozyme-dependent degradation
AU - Ma, Yuhong
AU - Yuan, Sen
AU - Tian, Xuezhang
AU - Lin, Shanchuan
AU - Wei, Shangmou
AU - Hu, Tongtong
AU - Chen, Shiyou
AU - Li, Xueqing
AU - Chen, Shuliang
AU - Wu, Dongcheng
AU - Wang, Min
AU - Guo, Deyin
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
KW - ABIN1
KW - HADC1
KW - lysosomal degradation
KW - p53
KW - proteasomal degradation
KW - ubiquitination
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U2 - 10.1002/jcb.26428
DO - 10.1002/jcb.26428
M3 - Article
C2 - 29058807
AN - SCOPUS:85039169980
SN - 0730-2312
VL - 119
SP - 3030
EP - 3043
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 4
ER -