TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA730586 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate TRIM33 facilitates the AR chromatin binding to directly regulate a transcription program that promotes PCa progression by protecting AR from Skp2-mediated ubiquitination and proteasomal degradation. We also show TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 is upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33 coactivated gene signature that is highly expressed in PCa tumors and predicts disease recurrence. Overall, our results reveal TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.
2022-05-05 | GSE174589 | GEO
Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate TRIM33 facilitates the AR chromatin binding to directly regulate a transcription program that promotes PCa progression by protecting AR from Skp2-mediated ubiquitination and proteasomal degradation. We also show TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 is upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33 coactivated gene signature that is highly expressed in PCa tumors and predicts disease recurrence. Overall, our results reveal TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.
2022-05-05 | GSE174109 | GEO
Project description:TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer
| PRJNA730585 | ENA
Project description:TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [ChIP-seq]
| PRJNA728353 | ENA
Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates Recql recruitment to chromatin and facilitates recovery of DNA synthesis. Deletion of Trim33 triggers chronic recruitment of Recql and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
2023-07-28 | GSE217521 | GEO
Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates Recql recruitment to chromatin and facilitates recovery of DNA synthesis. Deletion of Trim33 triggers chronic recruitment of Recql and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
2023-07-28 | GSE217523 | GEO
Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates Recql recruitment to chromatin and facilitates recovery of DNA synthesis. Deletion of Trim33 triggers chronic recruitment of Recql and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
2023-07-28 | GSE217520 | GEO
Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates Recql recruitment to chromatin and facilitates recovery of DNA synthesis. Deletion of Trim33 triggers chronic recruitment of Recql and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
2023-07-28 | GSE217519 | GEO
Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates Recql recruitment to chromatin and facilitates recovery of DNA synthesis. Deletion of Trim33 triggers chronic recruitment of Recql and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
2023-07-28 | GSE235671 | GEO
Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates E2f4 and Recql recruitment to chromatin and facilitates recovery of DNA replication. Deletion of Trim33 triggers chronic recruitment of Recql to chromatin and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
2023-07-24 | PXD037854 | Pride