Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate
Summary: The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that...
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Format: | Article |
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Elsevier
2023-10-01
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Series: | iScience |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223020412 |
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author | Ava M. Boston Abdulrahman M. Dwead Marwah M. Al-Mathkour Kezhan Khazaw Jin Zou Qiang Zhang Guangdi Wang Bekir Cinar |
author_facet | Ava M. Boston Abdulrahman M. Dwead Marwah M. Al-Mathkour Kezhan Khazaw Jin Zou Qiang Zhang Guangdi Wang Bekir Cinar |
author_sort | Ava M. Boston |
collection | DOAJ |
description | Summary: The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that SCML2 interacts with YAP1, as revealed by immunological assays and mass spectroscopy. We have demonstrated that the steroid hormone androgen regulates the interaction of SCML2 with YAP1 in human tumor cell models. Our proximity ligation assay and GST pulldown showed that SCML2 and YAP1 physically interacted with each other. Silencing SCML2 by RNAi changed the growth behaviors of cells in response to androgen signaling. Mechanistically, this phenomenon is attributed to the interplay between distinct chromatin modifications and transcriptional programs, likely coordinated by the opposing SCML2 and YAP1 activity. These findings suggest that YAP1 and SCML2 cooperate to regulate cell growth, cell survival, and tumor biology downstream of steroid hormones. |
first_indexed | 2024-03-11T15:22:08Z |
format | Article |
id | doaj.art-78e417cc88024ae884d334fc7ecab81b |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-03-11T15:22:08Z |
publishDate | 2023-10-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
spelling | doaj.art-78e417cc88024ae884d334fc7ecab81b2023-10-28T05:09:08ZengElsevieriScience2589-00422023-10-012610107964Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fateAva M. Boston0Abdulrahman M. Dwead1Marwah M. Al-Mathkour2Kezhan Khazaw3Jin Zou4Qiang Zhang5Guangdi Wang6Bekir Cinar7Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USADepartment of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USADepartment of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USADepartment of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USADepartment of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USADepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USADepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USADepartment of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA; Corresponding authorSummary: The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that SCML2 interacts with YAP1, as revealed by immunological assays and mass spectroscopy. We have demonstrated that the steroid hormone androgen regulates the interaction of SCML2 with YAP1 in human tumor cell models. Our proximity ligation assay and GST pulldown showed that SCML2 and YAP1 physically interacted with each other. Silencing SCML2 by RNAi changed the growth behaviors of cells in response to androgen signaling. Mechanistically, this phenomenon is attributed to the interplay between distinct chromatin modifications and transcriptional programs, likely coordinated by the opposing SCML2 and YAP1 activity. These findings suggest that YAP1 and SCML2 cooperate to regulate cell growth, cell survival, and tumor biology downstream of steroid hormones.http://www.sciencedirect.com/science/article/pii/S2589004223020412Molecular biologyCell biologyOmicsProteomics |
spellingShingle | Ava M. Boston Abdulrahman M. Dwead Marwah M. Al-Mathkour Kezhan Khazaw Jin Zou Qiang Zhang Guangdi Wang Bekir Cinar Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate iScience Molecular biology Cell biology Omics Proteomics |
title | Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate |
title_full | Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate |
title_fullStr | Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate |
title_full_unstemmed | Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate |
title_short | Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate |
title_sort | discordant interactions between yap1 and polycomb group protein scml2 determine cell fate |
topic | Molecular biology Cell biology Omics Proteomics |
url | http://www.sciencedirect.com/science/article/pii/S2589004223020412 |
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