The TEL gene products: nuclear phosphoproteins with DNA binding properties
Abstract
The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The predicted product of TEL harbours an amino acid region similar to the ETS DNA binding domain. We now report the isolation of the murine TEL cDNA and the characterization of the human TEL proteins. Human and murine TEL proteins are particularly homologous within their aminoterminal regions and their ETS domains. TEL proteins are nuclear and display specific DNA binding activity toward classical ETS binding sites. In addition, we show that TEL mRNAs initiate translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50 kDa and 57 kDa TEL proteins. In vivo, each of these primary translational products is modified by multiple phosphorylation events.
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TEL has an oligomerization domain in the N terminus that is conserved in several Ets members but not in PU.1.
“It also has the oligomerization domain (also called the pointed [PNT] domain, B domain, or HLH domain) in the N terminus that is conserved in several Ets members, but not in PU.1 (33, 39).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [39]
The TEL gene encodes at least two phosphoproteins, both isoforms being subject to common and distinct phosphorylation events.
“the TEL gene encodes at least two phosphoproteins, both isoforms being subject to common and distinct phosphorylation events (39).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [39]
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Mavrothalassitis, G., & Ghysdael, J. (2000) · Oncogene · doi:10.1038/sj.onc.1204045 · Cited by 153 · see citing works
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Ets transcription factors and human disease
Dittmer, J., & Nordheim, A. (1998) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(97)00039-5 · Cited by 136 · see citing works
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Quantification of Multiple Gene Expression in Individual CellsPreprint
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TEL-JAK2 transgenic mice develop T-cell leukemia
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“Similar to Yan, its closest relative in Drosophila, (53), ETV6 is subject to phosphorylation, sumoylation, and ubiquitination in vivo (31, 50, 54-57).”
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“This complex was competed by oligonucleotides containing a wild-type but not a mutant consensus ETS factor-binding site that TEL recognizes (52, 53, 77) (Fig.”
BackgroundTEL-JAK2 transgenic mice develop T-cell leukemia
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“Our results suggest that there may be multiple modified forms of two distinct TEL proteins, which is in accordance with observations reported by Poirel, Bernard, and coworkers (43).”
ResultCore binding factor genes and human leukemia.
Hart, S., & Foroni, L. (2002) · PubMed · Cited by 88 · see citing works
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion
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Self-citationModulation of TEL transcription activity by interaction with the ubiquitin-conjugating enzyme UBC9
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ETV6-related thrombocytopenia and leukemia predisposition
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“TEL is a member of the Ets family of transcriptional regulators and is widely expressed in all normal tissues [195].”
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“As expected, the wt construct produced two isoforms (50 and 57 kDa), starting from the first two in frame ATGs (codons 1 and 43) (Poirel et al., 1997).”
BackgroundAML1 gene over-expression in childhood acute lymphoblastic leukemia
Mikhail, F., Serry, K. A., Hatem, N., Mourad, Z., Farawela, H., Elkaffash, D. M., Coignet, L., & Nucifora, G. (2002) · Leukemia · doi:10.1038/sj.leu.2402399 · Cited by 72 · see citing works
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“This possibility may be supported by the fact that the TEL gene encodes at least two phosphoproteins, both isoforms being subject to common and distinct phosphorylation events (39).”
BackgroundInfluentialNormal and transforming functions of RUNX1: A perspective
Mikhail, F. M., Sinha, K. K., Saunthararajah, Y., & Nucifora, G. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20538 · Cited by 67 · see citing works
“TEL is a member of the ETS family of transcription regulators, is widely expressed in all normal tissues (Poirel et al., 1997), and is generally considered a repressor for its ability to interact with SMART, N-CoR, and Sin3A (Chakrabarti and Nucifora, 1999).”
BackgroundTootle, T. L., Lee, P. S., & Rebay, I. (2003) · Development · doi:10.1242/dev.00312 · Cited by 57 · see citing works
Fazio, G., Palmi, C., Rolink, A., Biondi, A., & Cazzaniga, G. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2778 · Cited by 55 · see citing works
Transcription factors and translocations in lymphoid and myeloid leukemia
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“ETV6-JAK2 (TEL-JAK2) fusion clones were constructed by polymerase chain reaction (PCR)-mediated amplification of the oligomerization domain of murine Etv6 (amino acids 43–154) (Poirel et al, 1997) and the 298 COOH-terminal residues of human Jak2 (Harpur et al, 1992).”
MethodTel-2 Is a Novel Transcriptional Repressor Related to the Ets Factor Tel/ETV-6
Gu, X., Shin, B., Akbarali, Y., Weiss, A., Boltax, J., Oettgen, P., & Libermann, T. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010070200 · Cited by 52 · see citing works
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Tel induces a G1 arrest and suppresses Ras-induced transformation
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“Tel is a phosphoprotein expressed in most cell types as two isoforms (Poirel et al., 1997).”
BackgroundTEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways
Kanie, T., Abe, A., Matsuda, T., Kuno, Y., Towatari, M., Yamamoto, T., Saito, H., Emi, N., & Naoe, T. (2004) · Leukemia · doi:10.1038/sj.leu.2403266 · Cited by 51 · see citing works
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A detailed transcriptional map of the chromosome 12p12 tumour suppressor locus
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“We thus examined whether hyperphosphorylated TEL still possesses EBS-specific DNA-binding properties like unmodified TEL does.”
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Zhou, M., Gao, L., Jing, Y., et al. (2012) · Annals of Hematology · doi:10.1007/s00277-012-1431-4 · Cited by 40 · see citing works
“etic regulatory factor [13, 14].”
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“In the case of Tel, the observed heterogeneity of Tel proteins in cells (37, 29, 43) can be accounted for by at least two posttranscriptional mechanisms—the use of an alternative initiation codon (37, 29) and alternative splicing (38; M.”
BackgroundTEL/AML1 shows dominant-negative effects over TEL as well as AML1
Gunji, H., Waga, K., Nakamura, F., Maki, K., Sasaki, K., Nakamura, Y., & Mitani, K. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.169 · Cited by 38 · see citing works
The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells
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“The antibodies used were the 4G10 antiphosphotyrosine antibody (Upstate Biotechnology, Inc.) the 9E10 anti-Myc antibody (Santa Cruz Biotechnology, Inc.) and an anti-TEL rabbit immunserum (Poirel et al., 1997).”
MethodSelf-citationAutoinhibition of ETV6 (TEL) DNA Binding: Appended Helices Sterically Block the ETS Domain
Coyne, H. J., De, S., Okon, M., Green, S. M., Bhachech, N., Graves, B. J., & McIntosh, L. P. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.05.010 · Cited by 36 · see citing works
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Functional regulation of TEL by p38-induced phosphorylation
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EVI1 in Leukemia and Solid Tumors
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Poirel, H. A., Lopez, R. G., Penard‐Lacronique, V., Della-Valle, V., Mauchauffé, M., Berger, R., Ghysdael, J., & Bernard, O. (2000) · Oncogene · doi:10.1038/sj.onc.1203830 · Cited by 34 · see citing works
“The smaller (M43) lacks a putative MAPK site found at serine 22 in the large form (M1) and both forms are transcriptional repressors of EBSdriven transcription (Chakrabarti and Nucifora, 1999; Fenrick et al., 1999; Lopez et al., 1999; Poirel et al., 1997; 1998).”
BackgroundSelf-citationRoukens, M. G., Alloul‐Ramdhani, M., Vertegaal, A. C. O., Anvarian, Z., Balog, C. I. A., Deelder, A. M., Hensbergen, P. J., & Baker, D. A. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01159-07 · Cited by 33 · see citing works
“Tel proteins were detected with a Tel antibody directed against the C terminus of Tel (highlighted with arrows) (20).”
BackgroundETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation
Gao, Y., He, X., Wu, X., Huang, Y., Toneyan, S., Ha, T., Ipsaro, J. J., Koo, P. K., Joshua‐Tor, L., Bailey, K. M., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-022-01060-1 · Cited by 35 · see citing works
ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease
Rasighaemi, P., & Ward, A. C. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.05.011 · Cited by 32 · see citing works
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TEL GENE REARRANGEMENTS IN MYELOID MALIGNANCY
Golub, T. R. (1997) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70490-1 · Cited by 27 · see citing works
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Hypoxia and estrogen co-operate to regulate gene expression in T-47D human breast cancer cells
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Waga, K., Nakamura, Y., Maki, K., Arai, H., Yamagata, T., Sasaki, K., Kurokawa, M., Hirai, H., & Mitani, K. (2003) · Oncogene · doi:10.1038/sj.onc.1206072 · Cited by 24 · see citing works
“TEL is a member of the ETS family transcription factors (Golub et al., 1994) that acts as a transcriptional repressor (Poirel et al., 1997; Lopez et al., 1999).”
BackgroundMethodInfluentialSawińska, M., & Ładoń, D. (2003) · Leukemia Research · doi:10.1016/s0145-2126(03)00160-7 · Cited by 24 · see citing works
“Throughout mouse embryonic development and within most human and mouse cell lines and tissues TEL gene expresses [33,47].”
BackgroundNguyen‐Khac, F., Della-Valle, V., Lopez, R. G., Ravet, E., Mauchauffé, M., Friedman, A. D., Huang, E. L., Fichelson, S., Ghysdael, J., & Bernard, O. (2006) · Oncogene · doi:10.1038/sj.onc.1209503 · Cited by 23 · see citing works
“TEL, Gal 4 and UAS-reporter vectors have been described previously (Poirel et al., 1997; Lopez et al., 1999).”
BackgroundSelf-citationFunctional analysis of a dominant-negative ΔETS TEL/ETV6 isoform
Sasaki, K., Nakamura, Y., Maki, K., Waga, K., Nakamura, F., Arai, H., Imai, Y., Hirai, H., & Mitani, K. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.03.172 · Cited by 22 · see citing works
Molecular mechanism of angiogenesis Transcription factors and their therapeutic relevance
Sato, Y. (2000) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(00)00067-x · Cited by 21 · see citing works
ETV6 (TEL1) regulates embryonic hematopoiesis in zebrafish
Rasighaemi, P., Onnebo, S. M. N., Liongue, C., & Ward, A. C. (2014) · Haematologica · doi:10.3324/haematol.2014.104091 · Cited by 21 · see citing works
Mutational analysis of ETV6 in prostate carcinoma
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“The DNA binding region is highly conserved between ets family members, and ETV6 displays DNA binding activity toward ets binding motifs [27].”
BackgroundTEL/ETV6 induces apoptosis in 32D cells through p53-dependent pathways
Yamagata, T., Maki, K., Waga, K., & Mitani, K. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.06.127 · Cited by 19 · see citing works
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Identification of the nuclear localization motif in the ETV6 (TEL) protein
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“As previously observed (2, 40), wild-type TEL formed a specific DNA-protein complex that emerged as a somewhat broad band possibly due to weak binding (Fig.”
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TEL Induces Aggregation in Transformed Cells and Induces Tube Formation in NIH3T3-UCLA Cells
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Comparative analysis of the ETV6 gene in vertebrate genomes from pufferfish to human
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“ETV6 has been shown to be hyperphosphorylated in vivo (Poirel et al., 1997).”
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“Both bind DNA in a sequence-specific fashion via their ETSDNA binding domain, and both also homotypically polymerize via a sterile alpha motif (SAM) domain (12,13,17).”
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- Authors
- Poirel, H., Oury, C., Carron, C., Duprez, E., Laabi, Y., Tsapis, A., Romana, S. P., Mauchauffe, M., Le Coniat, M., Berger, R., Ghysdael, J., & Bernard, O. A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- Oncogene
- Published
- 1997-01-23
- Volume
- 14
- Issue
- 3
- Pages
- 349-357
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2002377159
- Cited by
- 106
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 11.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Funders
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- ETS transcription factors, nuclear phosphoprotein, 21)(p13, childhood acute lymphoblastic leukemia, alternative translation initiation, hematologic malignancies
- MeSH terms
- ETS Translocation Variant 6 Protein, Animals, Base Sequence, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 21, Cloning, Molecular, DNA, DNA-Binding Proteins, Humans, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Phosphorylation, Repressor Proteins, RNA, Messenger, Transcription Factors, Translocation, Genetic, Tumor Cells, Cultured, Blotting, Western, Leukemia, B-Cell, In Situ Hybridization, Fluorescence, DNA, Complementary, COS Cells, Proto-Oncogene Proteins c-ets, Mice
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