Aryl sulfonamides induce degradation of aryl hydrocarbon receptor nuclear translocator through crl4dcaf15 e3 ligase

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Title
Aryl sulfonamides induce degradation of aryl hydrocarbon receptor nuclear translocator through crl4dcaf15 e3 ligase
Author(s)
Sung Ah Kim; Seung-Hyun Jo; Jin Hwa Cho; Min Yeong Yu; Ho Chul ShinJung Ae KimSung Goo ParkByoung Chul Park; Sunhong Kim; Jeong Hoon Kim
Bibliographic Citation
Molecules and Cells, vol. 43, no. 11, pp. 935-944
Publication Year
2020
Abstract
Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.
Keyword
aryl hydrocarbon receptor nuclear translocatoraryl sulfonamidecullin ring ubiquitin ligaseDDB1 and CUL4 associated factor 15E7820indisulam
ISSN
1016-8478
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.14348/molcells.2020.0122
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
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