Angaben zur Quelle [Bearbeiten]
Autor | Cory Abate-Shen |
Titel | Deregulated homebox gene expression in cancer: cause or consequence? |
Zeitschrift | Nature Reviews |
Verlag | Nature Publishing Group |
Ausgabe | 2 |
Datum | October 2002 |
Seiten | 777-785 |
DOI | 10.1038/nrc907 |
URL | http://hiccc.columbia.edu/lab/abate-shen/sites/abate-shen/files/useruploads/Abate-Shen_2002_Nat_Rev_Cancer.pdf |
Literaturverz. |
yes |
Fußnoten | yes |
Fragmente | 5 |
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The homeobox (HB) was first identified in the 1980s as a sequence motif that was shared among Drosophila homeotic genes (the HOM-C complex), where they play a key role in embryonic differentiation along the anterior–posterior (ap) axis, and is now known to be present in many genes in virtually all eukaryotic species (Stein et. al., 1996). It is estimated that the human genome contains at least 200 homeobox genes (Tupler et. al., 2001), of which only 39 are members of the HOX family. Unlike the HOM-C/HOX genes, which are organized in gene clusters, most homeobox genes are dispersed throughout the genome (Abate-Shen, 2002).
Abate-Shen, C. (2002). Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer 2, 777-785. Stein, S., Fritsch, R., Lemaire, L., and Kessel, M. (1996). Checklist: vertebrate homeobox genes. Mech Dev 55, 91-108. Tupler, R., Perini, G., and Green, M. R. (2001). Expressing the human genome. Nature 409, 832-833. |
The homeobox was first identified in the 1980s as a sequence motif that was shared among Drosophila HOMEOTIC GENES (the HOM-C complex), and is now known to be present in many genes in virtually all eukaryotic species1,2. [...] It is estimated that the human genome, for example, includes at least 200 homeobox genes3, of which only 39 are members of the HOX family. Unlike the HOM-C/HOX genes, which are organized on chromosome clusters, most homeobox genes are dispersed throughout the genome.
1. Duboule, D. (ed.) Guidebook to the Homeobox Genes (Oxford Univ. Press, New York, 1994). 2. Stein, S., Fritsch, R., Lemaire, L. & Kessel, M. Checklist: vertebrate homeobox genes. Mech. Dev. 55, 91–108 (1996). 3. Tupler, R., Perini, G. & Green, M. R. Expressing the human genome. Nature 409, 832–833 (2001). |
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Although individual members of homeobox families often share little sequence similarity other than the homeobox, some families have additional conserved sequence motifs that contribute to their distinct functional properties (Fig. 5) (Abate-Shen, 2002; Owens and Hawley, 2002) | Although individual members of homeobox families often share little sequence similarity other than the homeobox, some families have additional conserved sequence motifs that contribute to their distinct functional properties (BOX 3). |
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The source is given at the end of the two figure captions. However, both figures are copied and not "adapted". Furthermore, the extensive figure captions are also taken 1-to-1 from the source, which does not become clear from the references at all. |
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Functional diversity is also generated by additional conserved domains or motifs that occur in particular homeoprotein families. HOX proteins contain a hexapeptide (HP) motif-a short stretch of conserved residues that are responsible for mediating interactions with PBX homeoproteins. MSX proteins also have short stretches of conserved amino acids that flank the homeodomain, called the extended homeodomain (EHD), although their functions are unknown. PAX proteins contain an additional DNA-binding domain, known as the paired box. Members of the SIX family have a conserved amino-terminal domain called the Six domain, and LIM homeoproteins are named after a protein interaction motif, the LIM domain (Figure adapted from Abate-Shen, 2002). | Functional diversity is also generated by additional conserved domains or motifs that occur in particular homeoprotein families. HOX proteins contain a hexapeptide (HP) motif-a short stretch of conserved residues that are responsible for mediating interactions with PBX homeoproteins. MSX proteins also have short stretches of conserved amino acids that flank the homeodomain, called the extended homeodomain (EHD), although their functions are unknown. PAX proteins contain an additional DNA-binding domain, known as the paired box. Members of the SIX family have a conserved amino-terminal domain called the Six domain, and LIM homeoproteins are named after the protein interaction motif, the LIM domain. |
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CDX2 is normally expressed in the gut during development and adulthood. However, its expression is lost in colorectal tumors and corresponding carcinoma cell lines (Ee et. al., 1995; Hinoi et. al., 2003; Hinoi et. al., 2001). A role for the loss of Cdx2 expression in colorectal carcinoma development can be inferred from the frequent occurrence of adenomatous intestinal polyps in Cdx2 heterozygous mutant mice.
Ee, H. C., Erler, T., Bhathal, P. S., Young, G. P., and James, R. J. (1995). Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Am J Pathol 147, 586-592. Hinoi, T., Loda, M., and Fearon, E. R. (2003). Silencing of CDX2 expression in colon cancer via a dominant repression pathway. J Biol Chem 278, 44608-44616. Hinoi, T., Tani, M., Lucas, P. C., Caca, K., Dunn, R. L., Macri, E., Loda, M., Appelman, H. D., Cho, K. R., and Fearon, E. R. (2001). Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol 159, 2239-2248. |
CDX2 is normally expressed in the gut during development and adulthood52–54; however, its expression is lost in colorectal tumours and corresponding carcinoma cell lines32,55,56.A functional role for the loss of function of Cdx2 in colorectal carcinoma has been indicated by the frequent occurrence of ADENOMATOUS INTESTINAL POLYPS in Cdx2 heterozygous mutant mice57;
32. Ee, H. C., Erler, T., Bhathal, P. S., Young, G. P. & James, R. J. Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Am. J. Pathol. 147, 586–592 (1995). 52. James, R. & Kazenwadel, J. Homeobox gene expression in the intestinal epithelium of adult mice. J. Biol. Chem. 266, 3246–3251 (1991). 53. James, R., Erler, T. & Kazenwadel, J. Structure of the murine homeobox gene cdx-2. Expression in embryonic and adult intestinal epithelium. J. Biol. Chem. 269, 15229–15237 (1994). 54. Silberg, D. G., Swain, G. P., Suh, E. R. & Traber, P. G. Cdx1 and cdx2 expression during intestinal development. Gastroenterology 119, 961–971 (2000). 55. Mallo, G. V. et al. Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis. Int. J. Cancer 74, 35–44 (1997). 56. Hinoi, T. et al. Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am. J. Pathol. 159, 2239–2248 (2001). 57. Chawengsaksophak, K., James, R., Hammond, V. E., Kontgen, F. & Beck, F. Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 386, 84–87 (1997). [...] |
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