von Dr. Vijay Pal Singh Rawat
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| [1.] Vpr/Fragment 019 01 - Diskussion Zuletzt bearbeitet: 2014-04-05 16:25:15 Hindemith | Fontanari Krause 2006, Fragment, Gesichtet, SMWFragment, Schutzlevel sysop, Verschleierung, Vpr |
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| Untersuchte Arbeit: Seite: 19, Zeilen: 1-26 |
Quelle: Fontanari Krause 2006 Seite(n): 20, 21, Zeilen: 20: 19-32 - 21: 1-9 |
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| The failure of certain fusion genes to induce leukemia on their own in animal models as well as the fact that more than 50% of acute myeloid leukemias do not have apparent cytogenetic abnormalities, point to the role of point mutations in or, alternatively, the aberrant expression of proto-oncogenes in the development of leukemia. These observations also suggest that the aberrant expression of proto-oncogenes might be more common than is generally believed. The sheer number of ETV6 fusions in AML allows for the study of a diverse group of leukemias in which more than one of the aforementioned mechanisms might be operating. The t(12;13) translocation is particularly interesting in this regard as the expression of both the ETV6/CDX2 fusion gene as well as the ectopic expression of the CDX2 gene has been demonstrated.
1.6 ETV6 ETV6 (ETS variant gene 6) was originally called TEL, for translocation ets leukemia gene. ETV6 is a member of the ets (E-26 transforming specific) family of transcription factors. All ets family proteins share a conserved protein domain of about 88 amino acids in length, the so called ets domain (see Figure 10) (Bohlander SK 2005). The ets domain is a sequence specific DNA binding domain but it also mediates protein-protein interaction. The other evolutionarily conserved domain is the N terminally located pointed or SAM (sterile alpha motif) domain in the 652 amino acids of ETV6 (Bohlander SK 2005). This domain is also called HLH (helix loop helix) domain. It is found in yeast proteins and has been shown to be involved in homo and heterodimerization of transcription factors and in signal transducing proteins (e.g. of the MAPK pathway) (Fig.10). ETV6 contains two alternative translational start codons (position 1 and position 43), leading to the expression of two isoforms of ETV6. Bohlander S K (2005). ETV6: a versatile player in leukemogenesis.Semin Cancer Biol 15(3):162-74. |
The failure of certain fusion genes to induce leukemia on their own, in animal models, as well as the fact that more than 50% of acute myeloid leukemias do not have apparent cytogenetic abnormalities, point to the role of point mutations in or, alternatively, the aberrant expression of proto-oncogenes in the development of leukemia. These observations also suggest that the aberrant expression of proto-oncogenes might be more common than is generally believed.
The sheer number of ETV6 fusions in AML allows for the study of a diverse group of leukemias in which more than one of the aforementioned mechanisms might be operating. The t(6;12) translocation is one of several that involve ETV6, in this case ETV6 is fused to STL gene in a B-cell ALL cell line. 4.3. ETV6 ETV6 is a member of the ets (E-26 transforming specific) family of transcription factors. All ets family proteins share a highly conserved protein domain of about 88 amino acids in length the so-called ets domain. The ets domain is a sequence specific DNA binding domain but is [sic] also mediates protein-protein interaction (Figure 4.7, modified from Slupsky, 1998), it is [page 21] evolutionarily highly conserved and found in invertebrates such as Drosophila and C. elegans (Oikawa, 2003; Wasylyk, 1993). The other evolutionarily conserved domain in the 652 amino acids of ETV6 is the N-terminally located pointed or sterile alpha motif (SAM) domain (Figure 4.7). This domain is also called HLH domain and is even more highly conserved in evolution and found in many ets family member. It is found in yeast proteins and has been shown to be involved in homo and heterodimerization in transcription factors and in signal transducing proteins (e.g. of the MAPK pathway) (Grimshaw, 2004). ETV6 contains two alternative translational start codons (position 1 and position 43) leading to the expression of two isoforms of ETV6. |
The source is not given. Note that the text of the second part of the fragment can also be found in Bohlander (2005), see Vpr/Dublette/Fragment 019 13. However, despite the fact that Vpr mentions Bohlander (2005) in the text, the likely source is still the here documented Fontanari Krause (2006), because the text there is closer to Bohlander (2005), in particular containing text fragments not included in Vpr (e.g. the half-sentence: "and is even more highly conserved in evolution and found in many ets family member"), such that it is not likely that Fontanari Krause (2006) copied from Vpr, more likely is the other way round. It is also unlikely that both authors copied from Bohlander (2005) independently as there are passages in close proximity that can be found in Vpr and in Fontanari Krause (2006) but not in Bohlander (2005) |
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