Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC
The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here, we show that SRSF1 is a direct target of the transcription factor oncoprotein MYC. These two oncogenes are significantly coexpressed in lung carcinomas, and MYC knockdown downregulates SRS...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-02-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124711000118 |
| _version_ | 1811315049569976320 |
|---|---|
| author | Shipra Das Olga Anczuków Martin Akerman Adrian R. Krainer |
| author_facet | Shipra Das Olga Anczuków Martin Akerman Adrian R. Krainer |
| author_sort | Shipra Das |
| collection | DOAJ |
| description | The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here, we show that SRSF1 is a direct target of the transcription factor oncoprotein MYC. These two oncogenes are significantly coexpressed in lung carcinomas, and MYC knockdown downregulates SRSF1 expression in lung-cancer cell lines. MYC directly activates transcription of SRSF1 through two noncanonical E-boxes in its promoter. The resulting increase in SRSF1 protein is sufficient to modulate alternative splicing of a subset of transcripts. In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC's oncogenic activity, decreasing proliferation and anchorage-independent growth. These results suggest a mechanism for SRSF1 upregulation in tumors with elevated MYC and identify SRSF1 as a critical MYC target that contributes to its oncogenic potential by enabling MYC to regulate the expression of specific protein isoforms through alternative splicing. |
| first_indexed | 2024-04-13T11:23:19Z |
| format | Article |
| id | doaj.art-9354842146bf4e3085a1443a55804a89 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T11:23:19Z |
| publishDate | 2012-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9354842146bf4e3085a1443a55804a892022-12-22T02:48:45ZengElsevierCell Reports2211-12472012-02-011211011710.1016/j.celrep.2011.12.001Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYCShipra Das0Olga Anczuków1Martin Akerman2Adrian R. Krainer3Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USAThe SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here, we show that SRSF1 is a direct target of the transcription factor oncoprotein MYC. These two oncogenes are significantly coexpressed in lung carcinomas, and MYC knockdown downregulates SRSF1 expression in lung-cancer cell lines. MYC directly activates transcription of SRSF1 through two noncanonical E-boxes in its promoter. The resulting increase in SRSF1 protein is sufficient to modulate alternative splicing of a subset of transcripts. In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC's oncogenic activity, decreasing proliferation and anchorage-independent growth. These results suggest a mechanism for SRSF1 upregulation in tumors with elevated MYC and identify SRSF1 as a critical MYC target that contributes to its oncogenic potential by enabling MYC to regulate the expression of specific protein isoforms through alternative splicing.http://www.sciencedirect.com/science/article/pii/S2211124711000118 |
| spellingShingle | Shipra Das Olga Anczuków Martin Akerman Adrian R. Krainer Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC Cell Reports |
| title | Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC |
| title_full | Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC |
| title_fullStr | Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC |
| title_full_unstemmed | Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC |
| title_short | Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC |
| title_sort | oncogenic splicing factor srsf1 is a critical transcriptional target of myc |
| url | http://www.sciencedirect.com/science/article/pii/S2211124711000118 |
| work_keys_str_mv | AT shipradas oncogenicsplicingfactorsrsf1isacriticaltranscriptionaltargetofmyc AT olgaanczukow oncogenicsplicingfactorsrsf1isacriticaltranscriptionaltargetofmyc AT martinakerman oncogenicsplicingfactorsrsf1isacriticaltranscriptionaltargetofmyc AT adrianrkrainer oncogenicsplicingfactorsrsf1isacriticaltranscriptionaltargetofmyc |