Expression and function of Ets transcription factors in mammalian development: a regulatory network

Maroulakou, Ioanna G.; Bowe, Damon B.

doi:10.1038/sj.onc.1204039

Cited by 202 publications

(158 citation statements)

References 116 publications

(177 reference statements)

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“…These genes regulate development of hematopoietic stem cells and are implicated in adverse prognosis of both acute myeloid leukemia (AML) and ALL. [30][31][32] It is possible that high expression of ERG, BAALC, or WT1 signifies stem cell-like properties that protect these tumors against chemotherapy. In fact, T-ALL/ LBL with an ETP immunophenotype has a genetic profile more akin to normal hematopoietic and myeloid leukemic stem cells 33 and may carry FLT3-ITD mutation, a feature typically associated with AML.…”

Section: Discussionmentioning

confidence: 99%

Absence of terminal deoxynucleotidyl transferase expression identifies a subset of high-risk adult T-lymphoblastic leukemia/lymphoma

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Absence of terminal deoxynucleotidyl transferase expression identifies a subset of high-risk adult T-lymphoblastic leukemia/lymphoma

et al. 2013

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“…In this study, we identified ets-1D(III-VI), a novel ets-1 variant resulting from the alternative splicing of exons III to VI. This variant, first identified in HIG-82 rabbit synovial fibroblastic cells, was detected in many human tissues known for expressing Ets-1 (Rowe and Propst, 1992;Maroulakou and Bowe, 2000;Takai et al, 2006; Figure 1). The relative ratio of both ets-1 and ets-1D(III-VI) varied with cell and tissue type, suggesting tissue-specific effects of ets-1D(III-VI).…”

Section: Discussionmentioning

confidence: 99%

Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51

et al. 2009

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The transcription factor Ets-1 is implicated in various physiological processes and invasive pathologies. We identified a novel variant of ets-1, ets-1D(III-VI), resulting from the alternative splicing of exons III to VI. This variant encodes a 27 kDa isoform, named Ets-1 p27. Ets-1 p27 lacks the threonine-38 residue, the Pointed domain and the transactivation domain, all of which are required for the transactivation of Ets-1 target genes. Both inhibitory domains surrounding the DNA-binding domain are conserved, suggesting that Ets-1 p27, like the full-length Ets-1 p51 isoform, is autoinhibited for DNA binding. We showed that Ets-1 p27 binds DNA in the same way as Ets-1 p51 does and that it acts both at a transcriptional and a subcellular localization level, thereby constituting a dual-acting dominant negative of Ets-1 p51. Ets-1 p27 blocks Ets-1 p51-mediated transactivation of target genes and induces the translocation of Ets-1 p51 from the nucleus to the cytoplasm. Furthermore, Ets-1 p27 overexpression represses the tumor properties of MDA-MB-231 mammary carcinoma cells in correlation with the known implication of Ets-1 in various cellular mechanisms. Thus the dual-acting dominant-negative function of Ets-1 p27 gives to the Ets-1 p27/Ets-1 p51 ratio a determining effect on cell fate.

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“…Ets transcription factors are activators and repressors of transcription, important in the development of organisms throughout the Metazoa (9,10,22,38,48,50). Previous Ets1 knockout mice show partial perinatal lethality.…”

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confidence: 99%

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

Higuchi

Bartel

Masuya³

et al. 2007

Molecular and Cellular Biology

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Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1⌬VII (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1 ⌬VII isoform. Ets1⌬VII homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8 ؉ and CD8 ؉ CD4 ؉ thymocytes were observed. Lymphoid cell (CD19 ؉ , CD4 ؉ , and CD8 ؉ ) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1⌬VII mutants demonstrate lymphocyte maturation defects associated with misregulation of p16 Ink4a , p27Kip1 , and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis.

show abstract

Expression and function of Ets transcription factors in mammalian development: a regulatory network

Cited by 202 publications

References 116 publications

Absence of terminal deoxynucleotidyl transferase expression identifies a subset of high-risk adult T-lymphoblastic leukemia/lymphoma

Absence of terminal deoxynucleotidyl transferase expression identifies a subset of high-risk adult T-lymphoblastic leukemia/lymphoma

Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

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