| 1. |
- Osada, H, et al.
(författare)
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Association of erythroid transcription factors : complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1
- 1995
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Ingår i: Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:21, s. 9-9585
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Tidskriftsartikel (refereegranskat)abstract
- The RBTN2 LIM-domain protein, originally identified as an oncogenic protein in human T-cell leukemia, is essential for erythropoiesis. A possible role for RBTN2 in transcription during erythropoiesis has been investigated. Direct interaction of the RBTN2 protein was observed in vivo and in vitro with the GATA1 or -2 zinc-finger transcription factors, as well as with the basic helix-loop-helix protein TAL1. By using mammalian two-hybrid analysis, complexes involving RBTN2, TAL1, and GATA1, together with E47, the basic helix-loop-helix heterodimerization partner of TAL1, could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis, and the data suggest that variations in amounts of complexes involving RBTN2, TAL1, and GATA1 could be important for erythroid differentiation.
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| 2. |
- Osada, H, et al.
(författare)
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LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1
- 1997
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Ingår i: Leukemia. - 0887-6924. ; 11:Suppl 3, s. 12-307
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Tidskriftsartikel (refereegranskat)abstract
- The LIM-only protein Lmo2, originally identified as an oncogenic protein in human T cell leukemia, is essential for erythropoiesis. A possible role for Lmo2 in transcription during erythropoiesis has been investigated. Direct interaction of Lmo2 was observed in vitro and in vivo with the zinc finger transcription factor GATA-1, as well as with the basic helix-loop-helix (bHLH) transcription factor Tall. By using mammalian two-hybrid analysis, E47/Tall/Lmo2/GATA-1 protein complex could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis. This data suggest that variations in amounts of complexes involving Lmo2, Tall, and GATA-1 could be important for erythroid differentiation.
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| 3. |
- Rabbitts, T H, et al.
(författare)
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Chromosomal translocations and leukaemia : a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis
- 1997
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Ingår i: Leukemia. - 0887-6924. ; 11:Suppl 3, s. 2-271
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Tidskriftsartikel (refereegranskat)abstract
- The LMO2 gene associated with T cell acute leukaemia has been used as an example of a gene activated by association with the T cell receptor genes after chromosomal translocations. The gene is shown to encode a LIM protein which is involved in protein interactions and during normal haematopoiesis is necessary for erythroid development. LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development.
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| 4. |
- Sánchez-García, I, et al.
(författare)
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Functional diversity of LIM proteins : amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2
- 1995
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Ingår i: Oncogene. - 0950-9232. ; 10:7, s. 6-1301
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Tidskriftsartikel (refereegranskat)abstract
- The RBTN1 and RBTN2 genes are activated by distinct translocations involving chromosome 11 in some T cell acute leukaemias. The RBTN proteins belong to the LIM family which comprises proteins with one, two or three cysteine-rich LIM domains, sometimes together with homeodomains or protein kinase domains. The RBTN1 and RBTN2 proteins comprise only tandem LIM domains. We report that RBTN1 and RBTN2 proteins are capable of supporting transcriptional transactivation of specific reporter genes in transfection assays. The results, using intact proteins or fusions with the homeodomain of the heterologous protein Isl-1, show that this transcriptional activation ability resides in the NH2-terminal parts of both proteins. The use of yeast assays with RBTN2 shows that RBTN2 forms homodimers and that the NH2-terminal 27 amino acids are sufficient to facilitate transcriptional transactivation. These data expand the functional diversity of the LIM-domain protein family and they augment the previously defined relationship between chromosomal translocations and transcriptional activation.
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| 5. |
- Visintin, M, et al.
(författare)
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Selection of antibodies for intracellular function using a two-hybrid in vivo system
- 1999
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 96:21, s. 8-11723
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Tidskriftsartikel (refereegranskat)abstract
- Expression of antibodies inside cells has been used successfully to ablate protein function. This finding suggests that the technology should have an impact on disease treatment and in functional genomics where proteins of unknown function are predicted from genomic sequences. A major hindrance is the paucity of antibodies that function in eukaryotic cells, presumably because the antibodies fold incorrectly in the cytoplasm. To overcome this problem, we have developed an in vivo assay for functional intracellular antibodies using a two-hybrid approach. In this assay, antibody, as single-chain Fv (scFv) linked to a transcriptional transactivation domain, can interact with a target antigen, linked to a LexA-DNA binding domain, and thereby activate a reporter gene. We find that several characterized antibodies can bind their target antigen in eukaryotic cells in this two-hybrid format, and we have been able to isolate intracellular binders from among sets of scFv that can bind antigen in vitro. Furthermore, we show a model selection in which a single scFv was isolated from a mixture of half a million clones, indicating that this is a robust procedure that should facilitate capture of antibody specificities from complex mixtures. The approach can provide the basis for de novo selection of intracellular scFv from libraries, such as those made from spleen RNA after immunization with antigen, for intracellular analysis of protein function based only on genomic or cDNA sequences.
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| 6. |
- Miller, A, et al.
(författare)
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A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 10617-
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Tidskriftsartikel (refereegranskat)abstract
- Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin γ1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.
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| 7. |
- Mitelman, Felix, et al.
(författare)
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A short history of chromosome rearrangements and gene fusions in cancer
- 2015
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Ingår i: Chromosomal Translocations and Genome Rearrangements in Cancer. - Cham : Springer International Publishing. - 9783319199825 - 9783319199832 ; , s. 3-11
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Bokkapitel (refereegranskat)abstract
- The molecular characterization of recurrent chromosome aberrations in the early 1980s laid the foundation for gene fusion detection in cancer. This approach remained the unrivalled method to identify fusion genes for a quarter of a century and led to the detection of more than 700 neoplasia-associated fusion genes. The advancement of deep sequencing in the mid-2000s revolutionized the search for cytogenetically undetectable fusions, and such studies have dramatically changed the gene fusion landscape. A myriad of new gene fusions-more than 1,300-the great majority involving previously unsuspected genes, have been identified by sequencing-based analyses during the past 10 years.
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