NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy
Abstract The function and underlying mechanisms of p50 in the regulation of protein expression is much less studied because of its lacking of transactivation domain. In this study, we discovered a novel function of p50 in its stabilization of hypoxia-inducible factor 1α (HIF-1α) protein under the co...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05521-1 |
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| _version_ | 1832571215773958144 |
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| author | Junlan Zhu Shirui Huang Yang Li Jiheng Xu Ruifan Chen Mengxin Guo Xiaohui Qian Tengda Li Zhongxian Tian Honglei Jin Chuanshu Huang |
| author_facet | Junlan Zhu Shirui Huang Yang Li Jiheng Xu Ruifan Chen Mengxin Guo Xiaohui Qian Tengda Li Zhongxian Tian Honglei Jin Chuanshu Huang |
| author_sort | Junlan Zhu |
| collection | DOAJ |
| description | Abstract The function and underlying mechanisms of p50 in the regulation of protein expression is much less studied because of its lacking of transactivation domain. In this study, we discovered a novel function of p50 in its stabilization of hypoxia-inducible factor 1α (HIF-1α) protein under the condition of cells exposed to arsenic exposure. In p50-deficient (p50−/−) cells, the HIF-1α protein expression was impaired upon arsenic exposure, and such defect could be rescued by reconstitutional expression of p50. Mechanistic study revealed that the inhibition of autophagy-related gene 7 (ATG7)-dependent autophagy was in charge of p50-mediated HIF-1α protein stabilization following arsenic exposure. Moreover, p50 deletion promoted nucleolin (NCL) protein translation to enhance ATG7 mRNA transcription via directly binding transcription factor Sp1 mRNA and increase its stability. We further discovered that p50-mediated miR-494 upregulation gave rise to the inhibition of p50-mediated NCL translation by interacting with its 3’-UTR. These novel findings provide a great insight into the understanding of biomedical significance of p50 protein in arsenite-associated disease development and therapy. |
| format | Article |
| id | doaj-art-144b91a79d6744fea776965fa14cd265 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-144b91a79d6744fea776965fa14cd2652025-02-02T12:44:44ZengNature Publishing GroupCell Death and Disease2041-48892022-12-01131211210.1038/s41419-022-05521-1NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagyJunlan Zhu0Shirui Huang1Yang Li2Jiheng Xu3Ruifan Chen4Mengxin Guo5Xiaohui Qian6Tengda Li7Zhongxian Tian8Honglei Jin9Chuanshu Huang10Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityAbstract The function and underlying mechanisms of p50 in the regulation of protein expression is much less studied because of its lacking of transactivation domain. In this study, we discovered a novel function of p50 in its stabilization of hypoxia-inducible factor 1α (HIF-1α) protein under the condition of cells exposed to arsenic exposure. In p50-deficient (p50−/−) cells, the HIF-1α protein expression was impaired upon arsenic exposure, and such defect could be rescued by reconstitutional expression of p50. Mechanistic study revealed that the inhibition of autophagy-related gene 7 (ATG7)-dependent autophagy was in charge of p50-mediated HIF-1α protein stabilization following arsenic exposure. Moreover, p50 deletion promoted nucleolin (NCL) protein translation to enhance ATG7 mRNA transcription via directly binding transcription factor Sp1 mRNA and increase its stability. We further discovered that p50-mediated miR-494 upregulation gave rise to the inhibition of p50-mediated NCL translation by interacting with its 3’-UTR. These novel findings provide a great insight into the understanding of biomedical significance of p50 protein in arsenite-associated disease development and therapy.https://doi.org/10.1038/s41419-022-05521-1 |
| spellingShingle | Junlan Zhu Shirui Huang Yang Li Jiheng Xu Ruifan Chen Mengxin Guo Xiaohui Qian Tengda Li Zhongxian Tian Honglei Jin Chuanshu Huang NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy Cell Death and Disease |
| title | NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy |
| title_full | NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy |
| title_fullStr | NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy |
| title_full_unstemmed | NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy |
| title_short | NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy |
| title_sort | nf κb1 p50 stabilizes hif 1α protein through suppression of atg7 dependent autophagy |
| url | https://doi.org/10.1038/s41419-022-05521-1 |
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