YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
Innate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1β, and LPS. YAP9 const...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.914381/full |
| _version_ | 1828437517314031616 |
|---|---|
| author | Fengyuan Mandy Yang Liya Shen Dengxia Denise Fan Yaqin Bai Bizhou Li Jongdae Lee |
| author_facet | Fengyuan Mandy Yang Liya Shen Dengxia Denise Fan Yaqin Bai Bizhou Li Jongdae Lee |
| author_sort | Fengyuan Mandy Yang |
| collection | DOAJ |
| description | Innate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1β, and LPS. YAP9 constitutively interacts with another anti-inflammatory regulator A20 (TNFAIP3) to suppress inflammatory responses, but A20 and YAP can function only in the presence of the other. YAP9 uses a short stretch of amino acids in the proline-rich domain (PRD) and transactivation domain (TAD) suppress the inflammatory signaling while A20 mainly uses the zinc finger domain 7 (ZF7). Cell-penetrating synthetic PRD, TAD, and ZF7 peptides act as YAP9 and A20 mimetics respectively to suppress the proinflammatory responses at the cellular level and in mice. Our data uncover a novel anti-inflammatory axis and anti-inflammatory agents that can be developed to treat acute or chronic conditions where TNFα, IL-1β, or LPS plays a key role in initiating and/or perpetuating inflammation. |
| first_indexed | 2024-12-10T19:46:35Z |
| format | Article |
| id | doaj.art-48f7e41a702047eaa1e97b59273bb716 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T19:46:35Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-48f7e41a702047eaa1e97b59273bb7162022-12-22T01:35:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.914381914381YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentialsFengyuan Mandy YangLiya ShenDengxia Denise FanYaqin BaiBizhou LiJongdae LeeInnate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1β, and LPS. YAP9 constitutively interacts with another anti-inflammatory regulator A20 (TNFAIP3) to suppress inflammatory responses, but A20 and YAP can function only in the presence of the other. YAP9 uses a short stretch of amino acids in the proline-rich domain (PRD) and transactivation domain (TAD) suppress the inflammatory signaling while A20 mainly uses the zinc finger domain 7 (ZF7). Cell-penetrating synthetic PRD, TAD, and ZF7 peptides act as YAP9 and A20 mimetics respectively to suppress the proinflammatory responses at the cellular level and in mice. Our data uncover a novel anti-inflammatory axis and anti-inflammatory agents that can be developed to treat acute or chronic conditions where TNFα, IL-1β, or LPS plays a key role in initiating and/or perpetuating inflammation.https://www.frontiersin.org/articles/10.3389/fimmu.2022.914381/fullYAP9A20PRDTADZF7TNF |
| spellingShingle | Fengyuan Mandy Yang Liya Shen Dengxia Denise Fan Yaqin Bai Bizhou Li Jongdae Lee YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials Frontiers in Immunology YAP9 A20 PRD TAD ZF7 TNF |
| title | YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials |
| title_full | YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials |
| title_fullStr | YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials |
| title_full_unstemmed | YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials |
| title_short | YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials |
| title_sort | yap9 a20 complex suppresses proinflammatory responses and provides novel anti inflammatory therapeutic potentials |
| topic | YAP9 A20 PRD TAD ZF7 TNF |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.914381/full |
| work_keys_str_mv | AT fengyuanmandyyang yap9a20complexsuppressesproinflammatoryresponsesandprovidesnovelantiinflammatorytherapeuticpotentials AT liyashen yap9a20complexsuppressesproinflammatoryresponsesandprovidesnovelantiinflammatorytherapeuticpotentials AT dengxiadenisefan yap9a20complexsuppressesproinflammatoryresponsesandprovidesnovelantiinflammatorytherapeuticpotentials AT yaqinbai yap9a20complexsuppressesproinflammatoryresponsesandprovidesnovelantiinflammatorytherapeuticpotentials AT bizhouli yap9a20complexsuppressesproinflammatoryresponsesandprovidesnovelantiinflammatorytherapeuticpotentials AT jongdaelee yap9a20complexsuppressesproinflammatoryresponsesandprovidesnovelantiinflammatorytherapeuticpotentials |