The EWS/ATF1 fusion protein contains a dispersed activation domain that functions directly
Naturally occurring chromosomal fusion of the Ewings Sarcoma Oncogene (EWS) to distinct cellular transcription factors, produces aberrant transcriptional activators that function as dominant oncogenes. In Malignant Melanoma of Soft Parts the N-terminal region of EWS is fused to C-terminal region of...
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| Veröffentlicht in: | Oncogene 1998-03, Vol.16 (12), p.1625-1631 |
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| container_title | Oncogene |
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| creator | SHU PAN KOH YEE MING DUNN, T. A LI, K. K. C LEE, K. A. W |
| description | Naturally occurring chromosomal fusion of the Ewings Sarcoma Oncogene (EWS) to distinct cellular transcription factors, produces aberrant transcriptional activators that function as dominant oncogenes. In Malignant Melanoma of Soft Parts the N-terminal region of EWS is fused to C-terminal region of the cAMP-inducible transcription factor ATF1. The EWS/ATF1 fusion protein binds to ATF sites present in cAMP-responsive promoters via the ATF1 bZIP domain and activates transcription constitutively in a manner that is dependent on an activation domain (EAD) present in EWS. To further define the requirements for trans-activation we have performed mutational analysis of EWS/ATF1 in mammalian cells and report several new findings. First, trans-activation by EWS/ATF1 does not require dimerisation with other ATF family members present in mammalian cells. Second, in contrast to the earlier suggestion of an allosteric role, the EAD can act directly. Third, determinants of trans-activation are dispersed throughout the EAD and cooperate synergistically to produce potent trans-activation. We also report that the region of EWS containing the EAD can activate transcription in Yeast. This latter finding might enable a genetic approach to understanding the mechanism of transcriptional activation by EWS and development of high-throughput screens for EWS inhibitors. |
| doi_str_mv | 10.1038/sj.onc.1201671 |
| format | Article |
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First, trans-activation by EWS/ATF1 does not require dimerisation with other ATF family members present in mammalian cells. Second, in contrast to the earlier suggestion of an allosteric role, the EAD can act directly. Third, determinants of trans-activation are dispersed throughout the EAD and cooperate synergistically to produce potent trans-activation. We also report that the region of EWS containing the EAD can activate transcription in Yeast. This latter finding might enable a genetic approach to understanding the mechanism of transcriptional activation by EWS and development of high-throughput screens for EWS inhibitors.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1201671</identifier><identifier>PMID: 9569031</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Allosteric properties ; Amino Acid Sequence ; Binding Sites - genetics ; Biological and medical sciences ; Choriocarcinoma - pathology ; Consensus Sequence ; Cyclic AMP ; Dimerization ; Diseases of the osteoarticular system ; DNA Mutational Analysis ; Ewings sarcoma ; Fusion protein ; Humans ; Mammalian cells ; Medical sciences ; Melanoma ; Oncogene Proteins, Fusion - genetics ; Oncogene Proteins, Fusion - metabolism ; Oncogene Proteins, Fusion - physiology ; Repetitive Sequences, Nucleic Acid ; Saccharomyces cerevisiae - genetics ; Sarcoma ; Transcription activation ; Transcription Factors ; Transcriptional Activation - physiology ; Tumor Cells, Cultured ; Tumors of striated muscle and skeleton</subject><ispartof>Oncogene, 1998-03, Vol.16 (12), p.1625-1631</ispartof><rights>1998 INIST-CNRS</rights><rights>Macmillan Publishers Limited 1998.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-191303ceb30cade4f4b531ff31cf263fba1f14c784a87210fae9b45d214a155c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2198197$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9569031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SHU PAN</creatorcontrib><creatorcontrib>KOH YEE MING</creatorcontrib><creatorcontrib>DUNN, T. A</creatorcontrib><creatorcontrib>LI, K. K. C</creatorcontrib><creatorcontrib>LEE, K. A. W</creatorcontrib><title>The EWS/ATF1 fusion protein contains a dispersed activation domain that functions directly</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Naturally occurring chromosomal fusion of the Ewings Sarcoma Oncogene (EWS) to distinct cellular transcription factors, produces aberrant transcriptional activators that function as dominant oncogenes. In Malignant Melanoma of Soft Parts the N-terminal region of EWS is fused to C-terminal region of the cAMP-inducible transcription factor ATF1. The EWS/ATF1 fusion protein binds to ATF sites present in cAMP-responsive promoters via the ATF1 bZIP domain and activates transcription constitutively in a manner that is dependent on an activation domain (EAD) present in EWS. To further define the requirements for trans-activation we have performed mutational analysis of EWS/ATF1 in mammalian cells and report several new findings. First, trans-activation by EWS/ATF1 does not require dimerisation with other ATF family members present in mammalian cells. Second, in contrast to the earlier suggestion of an allosteric role, the EAD can act directly. Third, determinants of trans-activation are dispersed throughout the EAD and cooperate synergistically to produce potent trans-activation. We also report that the region of EWS containing the EAD can activate transcription in Yeast. This latter finding might enable a genetic approach to understanding the mechanism of transcriptional activation by EWS and development of high-throughput screens for EWS inhibitors.</description><subject>Allosteric properties</subject><subject>Amino Acid Sequence</subject><subject>Binding Sites - genetics</subject><subject>Biological and medical sciences</subject><subject>Choriocarcinoma - pathology</subject><subject>Consensus Sequence</subject><subject>Cyclic AMP</subject><subject>Dimerization</subject><subject>Diseases of the osteoarticular system</subject><subject>DNA Mutational Analysis</subject><subject>Ewings sarcoma</subject><subject>Fusion protein</subject><subject>Humans</subject><subject>Mammalian cells</subject><subject>Medical sciences</subject><subject>Melanoma</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncogene Proteins, Fusion - metabolism</subject><subject>Oncogene Proteins, Fusion - physiology</subject><subject>Repetitive Sequences, Nucleic Acid</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Sarcoma</subject><subject>Transcription activation</subject><subject>Transcription Factors</subject><subject>Transcriptional Activation - physiology</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors of striated muscle and skeleton</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1r3DAQxUVpSTdpr70VDC29eaPRp3UMIWkKgR66pdCLkGWJePHKW40cyH9fLTE59NLTwLzfPGbmEfIB6BYo7y5xv52T3wKjoDS8IhsQWrVSGvGabKiRtDWMs7fkHHFPKdWGsjNyZqQylMOG_N49hObm14_Lq90tNHHBcU7NMc8ljKnxcypuTNi4ZhjxGDKGoXG-jI-unLhhPlS5KQ-u1NHkT02saA6-TE_vyJvoJgzv13pBft7e7K7v2vvvX79dX923nuuutGCAU-5Dz6l3QxBR9JJDjBx8ZIrH3kEE4XUnXKcZ0OiC6YUcGAgHUnp-Qb48-9a1_ywBiz2M6MM0uRTmBa02HVNC6f-CoFinpFAV_PQPuJ-XnOoRtjpB_afSolLbZ8rnGTGHaI95PLj8ZIHaUzYW97ZmY9ds6sDH1XbpD2F4wdcwqv551R16N8Xskh_xBWNgOjCa_wXvKJcG</recordid><startdate>19980326</startdate><enddate>19980326</enddate><creator>SHU PAN</creator><creator>KOH YEE MING</creator><creator>DUNN, T. 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A</au><au>LI, K. K. C</au><au>LEE, K. A. W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The EWS/ATF1 fusion protein contains a dispersed activation domain that functions directly</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>1998-03-26</date><risdate>1998</risdate><volume>16</volume><issue>12</issue><spage>1625</spage><epage>1631</epage><pages>1625-1631</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Naturally occurring chromosomal fusion of the Ewings Sarcoma Oncogene (EWS) to distinct cellular transcription factors, produces aberrant transcriptional activators that function as dominant oncogenes. In Malignant Melanoma of Soft Parts the N-terminal region of EWS is fused to C-terminal region of the cAMP-inducible transcription factor ATF1. The EWS/ATF1 fusion protein binds to ATF sites present in cAMP-responsive promoters via the ATF1 bZIP domain and activates transcription constitutively in a manner that is dependent on an activation domain (EAD) present in EWS. To further define the requirements for trans-activation we have performed mutational analysis of EWS/ATF1 in mammalian cells and report several new findings. First, trans-activation by EWS/ATF1 does not require dimerisation with other ATF family members present in mammalian cells. Second, in contrast to the earlier suggestion of an allosteric role, the EAD can act directly. Third, determinants of trans-activation are dispersed throughout the EAD and cooperate synergistically to produce potent trans-activation. We also report that the region of EWS containing the EAD can activate transcription in Yeast. 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| issn | 0950-9232 1476-5594 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Allosteric properties Amino Acid Sequence Binding Sites - genetics Biological and medical sciences Choriocarcinoma - pathology Consensus Sequence Cyclic AMP Dimerization Diseases of the osteoarticular system DNA Mutational Analysis Ewings sarcoma Fusion protein Humans Mammalian cells Medical sciences Melanoma Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - metabolism Oncogene Proteins, Fusion - physiology Repetitive Sequences, Nucleic Acid Saccharomyces cerevisiae - genetics Sarcoma Transcription activation Transcription Factors Transcriptional Activation - physiology Tumor Cells, Cultured Tumors of striated muscle and skeleton |
| title | The EWS/ATF1 fusion protein contains a dispersed activation domain that functions directly |
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