HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities
Summary: Hedgehog (Hh) signaling mediated by transcription factor Ci/Gli plays a vital role in embryonic development and adult tissue homeostasis in invertebrates and vertebrates, whose dysregulation leads to many human disorders, including cancer. However, till now, cofactors of Ci/Gli which can af...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223014116 |
| _version_ | 1797776642810052608 |
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| author | Yuxue Gao Zhaoliang Shan Chunhua Jian Ying Wang Xia Yao Shengnan Li Xiuxiu Ti Guochun Zhao Chen Liu Qing Zhang |
| author_facet | Yuxue Gao Zhaoliang Shan Chunhua Jian Ying Wang Xia Yao Shengnan Li Xiuxiu Ti Guochun Zhao Chen Liu Qing Zhang |
| author_sort | Yuxue Gao |
| collection | DOAJ |
| description | Summary: Hedgehog (Hh) signaling mediated by transcription factor Ci/Gli plays a vital role in embryonic development and adult tissue homeostasis in invertebrates and vertebrates, whose dysregulation leads to many human disorders, including cancer. However, till now, cofactors of Ci/Gli which can affect tumorigenesis are not well known. Here, through genetic screen, we find overexpression of active Ci alone is not sufficient to generate tumor-like eye phenotype in Drosophila, however, its overexpression combined with knockdown of hib causes a striking tumor-like big eye phenotype. Mechanistically, HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA polymerase II (RNAPII) components Rpb3/Rpb7 stabilities in E3 ligase dependent manner. In addition, Ci/Gli can promote HIB/SPOP-mediated Rpb7/Rpb3 degradation. Taken together, our results indicate Ci/Gli needs to hook up with suitable RNAPII together to achieve the tumor-like eye phenotype and HIB/SPOP plays dual roles through controlling Ci/Gli and Rpb3/Rpb7 protein stabilities to temper Ci/Gli/RNAPII-mediated tumorigenesis. |
| first_indexed | 2024-03-12T22:52:50Z |
| format | Article |
| id | doaj.art-3e725c33674a43a09e31553af962a6b8 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:52:50Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3e725c33674a43a09e31553af962a6b82023-07-20T04:39:01ZengElsevieriScience2589-00422023-08-01268107334HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilitiesYuxue Gao0Zhaoliang Shan1Chunhua Jian2Ying Wang3Xia Yao4Shengnan Li5Xiuxiu Ti6Guochun Zhao7Chen Liu8Qing Zhang9State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, ChinaDepartment of Medical Genetics, Nanjing Medical University, Nanjing 211166, China; Corresponding authorState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing 210061, China; Corresponding authorSummary: Hedgehog (Hh) signaling mediated by transcription factor Ci/Gli plays a vital role in embryonic development and adult tissue homeostasis in invertebrates and vertebrates, whose dysregulation leads to many human disorders, including cancer. However, till now, cofactors of Ci/Gli which can affect tumorigenesis are not well known. Here, through genetic screen, we find overexpression of active Ci alone is not sufficient to generate tumor-like eye phenotype in Drosophila, however, its overexpression combined with knockdown of hib causes a striking tumor-like big eye phenotype. Mechanistically, HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA polymerase II (RNAPII) components Rpb3/Rpb7 stabilities in E3 ligase dependent manner. In addition, Ci/Gli can promote HIB/SPOP-mediated Rpb7/Rpb3 degradation. Taken together, our results indicate Ci/Gli needs to hook up with suitable RNAPII together to achieve the tumor-like eye phenotype and HIB/SPOP plays dual roles through controlling Ci/Gli and Rpb3/Rpb7 protein stabilities to temper Ci/Gli/RNAPII-mediated tumorigenesis.http://www.sciencedirect.com/science/article/pii/S2589004223014116GeneticsCell biologyModel organism |
| spellingShingle | Yuxue Gao Zhaoliang Shan Chunhua Jian Ying Wang Xia Yao Shengnan Li Xiuxiu Ti Guochun Zhao Chen Liu Qing Zhang HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities iScience Genetics Cell biology Model organism |
| title | HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities |
| title_full | HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities |
| title_fullStr | HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities |
| title_full_unstemmed | HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities |
| title_short | HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities |
| title_sort | hib spop inhibits ci gli mediated tumorigenesis by modulating the rna polymerase ii components stabilities |
| topic | Genetics Cell biology Model organism |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223014116 |
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