Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression

Kim, C. A.

doi:10.1093/emboj/20.15.4173

Cited by 239 publications

(347 citation statements)

References 56 publications

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“…The TEL moiety, which is present and functional in the TEL-ARNT fusion protein, has been shown to possess both strong polymerization and transcriptional repression properties (Jousset et al, 1997;Lacronique et al, 1997;Salomon-Nguyen et al, 2000;Kim et al, 2001). To investigate whether oligomerization or repression properties would be important for the TEL-ARNT activity, we fused a Gal4 DNA binding domain with the …”

Section: Functional Analyses Of the Tel-arnt Fusion Proteinmentioning

confidence: 99%

“…The largest class of TEL's partner genes encodes protein tyrosine kinases whose catalytic domains are fused to the amino-terminal part of TEL. The TEL moiety induces polymerization of the fusion proteins, leading to constitutive kinase activity Jousset et al, 1997;Lacronique et al, 1997;Kim et al, 2001). The other class of TEL's partner genes encodes transcription factors such as RUNX1/AML1, which codes for a DNA binding subunit of the core binding factor (CBF; Speck, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation

et al. 2006

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The transcription factor hypoxia inducible factor 1 (HIF1), an HIF1a-aryl hydrocarbon receptor nuclear translocator (ARNT) dimeric factor, is essential to the cellular response to hypoxia. We described a t(1;12)(q21;p13) chromosomal translocation in human acute myeloblastic leukemia that involves the translocated Ets leukemia (TEL/ETV6) and the ARNT genes and results in the expression of a TEL-ARNT fusion protein.Functional studies show that TEL-ARNT interacts with HIF1a and the complex binds to consensus hypoxia response element. In low oxygen tension conditions, the HIF1a/TEL-ARNT complex does not activate transcription but exerts a dominant-negative effect on normal HIF1 activity. Differentiation of normal human CD34 þ progenitors cells along all the erythrocytic, megakaryocytic and granulocytic pathways was accelerated in low versus high oxygen tension conditions. Murine 32Dcl3 myeloid cells also show accelerated granulocytic differentiation in low oxygen tension in response to granulocyte colony-stimulating factor. Interestingly, stable expression of the TEL-ARNT in 32Dcl3 subclones resulted in impaired HIF1-mediated transcriptional response and inhibition of differentiation enhancement in hypoxic conditions. Taken together, our results underscore the role of oxygen tension in the modulation of normal hematopoietic differentiation, whose targeting can participate in human malignancies.

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Section: Functional Analyses Of the Tel-arnt Fusion Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation

et al. 2006

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“…It contains two functional domains: the helix-loop-helix (HLH) domain (also called the pointed domain) at the N-terminus and the ETS domain at the C-terminus. The HLH domain is necessary for homodimerization (Kim et al, 2001) and heterodimerization with other ETS family members such as FLI-1 Kwiatkowski et al, 1998) or TEL2 Gu et al, 2001). The ETS domain is responsible for DNA binding to the ETS-binding consensus site (EBS) that contains a purine-rich GGAA/T core motif.…”

Section: Introductionmentioning

confidence: 99%

Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells

et al. 2003

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TEL belongs to a member of the ETS family transcription factors that represses transcription of target genes such as FLI-1. Although TEL is essential for establishing hematopoiesis in neonatal bone marrow, its role in erythroid lineage is not understood. To investigate a role for TEL in erythroid differentiation, we introduced TEL into mouse erythroleukemia (MEL) cells. Overexpressing wild-type-TEL in MEL cells enhanced differentiation induced by hexamethylene bisacetamide or dimethylsulfoxide, as judged by the increased levels of erythroidspecific d-aminolevulinate synthase and b-globin mRNAs. TEL bound to a corepressor mSin3A through the helixloop-helix domain. A TEL mutant lacking this domain still bound to the ETS binding site, but lost its transrepressional effect. This mutant completely blocked erythroid differentiation in MEL cells. Moreover, it showed dominant-negative effects over TEL-mediated transcriptional repression and acceleration of erythroid differentiation. Endogenous TEL mRNA was found to increase during the first 3 days in differentiating MEL cells and drastically decrease thereafter. All these data suggest that TEL might play some role in erythroid cell differentiation.

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“…Phylogenetic analysis indicates that the SAM domain of SOP-2 belongs to a new nematode-specific SAM domain subfamily, which also includes the SAM domain of K04C1.2 and is more closely related to the SAM/PNT than to the SPM subfamiliy 3 . Nonetheless, the crystal structure shows that the SAM domains of PH and TEL form identical head-to-tail, left-handed helical polymers 12,13 , and the SAM domain of TEL is also required for its binding to UBC-9 and localization to nuclear bodies 14 . To correlate the functional properties of these SAM domains with their effects on nuclear localization, we undertook a series of domain-swapping experiments.…”

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confidence: 99%

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

et al. 2004

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Figure 1Interaction of SOP-2 with UBC-9 and sumoylation. (a) Results of yeast two-hybrid screens using the C terminus of SOP-2 as bait. The strength of the protein interaction is graded on the basis of comparison with controls: human Rb and E2F-1 interaction (+, faint blue color after 24 h in X-gal assay) and rat c-Fos and mouse c-Jun interaction (+++, blue color within 1 h in X-gal assay). (b) Interaction of the wild-type SOP-2 SAM domain with itself, with the SOP-2(bx91) mutant protein and with UBC-9. The bx91 mutation substantially reduces its interaction with UBC-9 but not with the wild-type SOP-2 SAM domain. (c) In vitro and in vivo sumoylation of SOP-2. In vitro sumoylation was carried out using labeled SOP-2 and purified sumoylation components. In vivo sumoylation of hemagglutinin-tagged SOP-2 and the SOP-2(bx91) mutant was done after transfection and expression in mammalian U2OS cells. Cell lysates were analyzed by immunoprecipitation (IP) with antibody to SUMO and western blotting with antibody to hemagglutinin.

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Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression

Cited by 239 publications

References 56 publications

Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation

Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation

Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

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