PMID: 8943060Nov 26, 1996Paper

The AML1/ETO fusion protein activates transcription of BCL-2

Proceedings of the National Academy of Sciences of the United States of America
L KlampferS D Nimer

Abstract

The AML1 gene, located on chromosome 21, is involved in several distinct chromosomal translocations in human leukemia. In t(8;21) acute myelogenous leukemia (AML), the AML1 gene is juxtaposed to the ETO gene located on chromosome 8, generating an AML1/ETO fusion protein. Both AML1/ETO and the AML1 proteins recognize the same consensus DNA-binding motif (TGT/CGGT), which is found in the promoters of several genes involved in hematopoiesis. We found that two myeloid leukemia cell lines with the t(8;21) translocation, Kasumi and SKNO-1, have elevated levels of BCL-2 protein compared with other myeloid cell lines. In addition, we identified a consensus AML1 binding site in the BCL-2 promoter. Thus far, AML1/ETO has been shown to dominantly repress its target genes; however, we found that AML1/ETO activates transcription of the BCL-2 gene in U937 cells. This activation requires the presence of both the runt homology domain (rhd) and the C-terminal portion of AML1/ETO. We demonstrated sequence specific binding of both AML1A and AML1/ETO to the TGTGGT sequence in the BCL-2 promoter and showed that the AML1 binding site is required for responsiveness to AML1/ETO. Interestingly, AML1A and AML1B do not modulate the activity of the BCL-2 ...Continue Reading

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Citations

Nov 28, 2001·International Journal of Hematology·R B Lorsbach, J R Downing
Aug 10, 2012·Frontiers of Medicine·Megan A HatlenStephen D Nimer
Dec 21, 2000·Current Oncology Reports·A JakubowiakS D Nimer
May 4, 2011·International Journal of Hematology·Susumu Goyama, James C Mulloy
Jan 17, 2002·Leukemia Research·Chava PerryHermona Soreq
Jan 14, 2000·Leukemia Research·E J DannJ D Rowley
Oct 14, 2003·Cancer Genetics and Cytogenetics·Sílvia CasasSakari Knuutila
Jul 14, 1998·Gene·J K Wolford, M Prochazka
Apr 20, 2001·Critical Reviews in Oncology/hematology·H H Sedlacek
May 3, 2005·Nature Reviews. Cancer·Karen BlythJames C Neil
Sep 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emmanuelle PasseguéIrving L Weissman
Jan 6, 2000·The Australian and New Zealand Journal of Psychiatry·H K ManjiR H Lenox
Jul 21, 2001·Molecular and Cellular Biology·S A BurelD E Zhang
Jan 1, 1997·Annual Review of Genetics·I Sánchez-García
Aug 28, 2013·The Journal of Clinical Investigation·Susumu GoyamaJames C Mulloy
Jan 25, 2013·International Journal of Molecular Sciences·Stefano Rossetti, Nicoletta Sacchi
Dec 1, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ming YanDong-Er Zhang
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·T MiyamotoK Akashi
Jan 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yue-Ying WangSai-Juan Chen
Feb 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·James C MulloyStephen D Nimer
Oct 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hatem E SabaawyDennis D Hickstein
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·S McNeilG S Stein
Sep 24, 2011·Advances in Hematology·Flora TzifiAndreas Scorilas
Mar 20, 2003·Cancer Investigation·Joäelle MichaudRobert Escher

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