The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway
Summary: Circadian clock controls daily behavior and physiology. The activity of various signaling pathways affects clock gene expression. Here, we show that the core circadian clock gene CRY1 is a direct target of the Hippo pathway effector YAP. YAP binds to TEADs and occupies the proximal promoter...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-08-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223015262 |
| _version_ | 1797753911371628544 |
|---|---|
| author | Abdelhalim Azzi Zhipeng Tao Yang Sun Hannah Erb Carla Guarino Xu Wu |
| author_facet | Abdelhalim Azzi Zhipeng Tao Yang Sun Hannah Erb Carla Guarino Xu Wu |
| author_sort | Abdelhalim Azzi |
| collection | DOAJ |
| description | Summary: Circadian clock controls daily behavior and physiology. The activity of various signaling pathways affects clock gene expression. Here, we show that the core circadian clock gene CRY1 is a direct target of the Hippo pathway effector YAP. YAP binds to TEADs and occupies the proximal promoter regions of CRY1, positively regulating its transcription. Interestingly, we further identified that CRY1 acts in a feedback loop to fine-tune Hippo pathway activation by modulating the expression of YAP and MOB1. Indeed, loss of CRY1 results in enhanced YAP activation. Consistently, we found that YAP levels and activity control clock gene expression and oscillation in synchronized cells. Furthermore, in breast cancer cells, CRY1 downregulation causes YAP/TAZ hyperactivation and enhanced DNA damage. Together, our findings provide a direct mechanistic link between the Hippo pathway and the circadian clock, where CRY1 and Hippo components form an orchestrated signaling network that influences cell growth and circadian rhythm. |
| first_indexed | 2024-03-12T17:25:48Z |
| format | Article |
| id | doaj.art-afbb677b1b4f4b4eba0fa2a4d4ebd213 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T17:25:48Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-afbb677b1b4f4b4eba0fa2a4d4ebd2132023-08-05T05:17:43ZengElsevieriScience2589-00422023-08-01268107449The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathwayAbdelhalim Azzi0Zhipeng Tao1Yang Sun2Hannah Erb3Carla Guarino4Xu Wu5Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Corresponding authorCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USACutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USACutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USACutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USACutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Corresponding authorSummary: Circadian clock controls daily behavior and physiology. The activity of various signaling pathways affects clock gene expression. Here, we show that the core circadian clock gene CRY1 is a direct target of the Hippo pathway effector YAP. YAP binds to TEADs and occupies the proximal promoter regions of CRY1, positively regulating its transcription. Interestingly, we further identified that CRY1 acts in a feedback loop to fine-tune Hippo pathway activation by modulating the expression of YAP and MOB1. Indeed, loss of CRY1 results in enhanced YAP activation. Consistently, we found that YAP levels and activity control clock gene expression and oscillation in synchronized cells. Furthermore, in breast cancer cells, CRY1 downregulation causes YAP/TAZ hyperactivation and enhanced DNA damage. Together, our findings provide a direct mechanistic link between the Hippo pathway and the circadian clock, where CRY1 and Hippo components form an orchestrated signaling network that influences cell growth and circadian rhythm.http://www.sciencedirect.com/science/article/pii/S2589004223015262Gene networkMolecular interactionTranscriptomics |
| spellingShingle | Abdelhalim Azzi Zhipeng Tao Yang Sun Hannah Erb Carla Guarino Xu Wu The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway iScience Gene network Molecular interaction Transcriptomics |
| title | The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway |
| title_full | The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway |
| title_fullStr | The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway |
| title_full_unstemmed | The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway |
| title_short | The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway |
| title_sort | circadian clock protein cryptochrome 1 is a direct target and feedback regulator of the hippo pathway |
| topic | Gene network Molecular interaction Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223015262 |
| work_keys_str_mv | AT abdelhalimazzi thecircadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT zhipengtao thecircadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT yangsun thecircadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT hannaherb thecircadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT carlaguarino thecircadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT xuwu thecircadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT abdelhalimazzi circadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT zhipengtao circadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT yangsun circadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT hannaherb circadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT carlaguarino circadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway AT xuwu circadianclockproteincryptochrome1isadirecttargetandfeedbackregulatorofthehippopathway |