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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 935 - 944 (10page)
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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.
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참고문헌 (39)
참고문헌 신청
Abel, J. / 2010 / An introduction to the molecular basics of aryl hydrocarbon receptor biology / Biol. Chem 391:1235~1248
Assi, R. / 2018 / Final results of a phase 2, open-label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome / Cancer 124:2758~2765
Bosu, D. R. / 2008 / Cullin-RING ubiquitin ligases : global regulation and activation cycles / Cell Div 3:7
Bussiere, D. E. / 2020 / Structural basis of indisulammediated RBM39 recruitment to DCAF15 E3 ligase complex / Nat. Chem. Biol 16:15~23
Du, X. / 2019 / Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820 / Structure 27:1625~1633
Assi, R. / 2018 / Final results of a phase 2, open-label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome / Cancer 124:2758~2765
Bosu, D. R. / 2008 / Cullin-RING ubiquitin ligases : global regulation and activation cycles / Cell Div 3:7
Bussiere, D. E. / 2020 / Structural basis of indisulammediated RBM39 recruitment to DCAF15 E3 ligase complex / Nat. Chem. Biol 16:15~23
Du, X. / 2019 / Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820 / Structure 27:1625~1633
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