LIM domain proteins in leukaemia and development.
T cell acute leukaemias involve a number of different classes of oncogenes. A group of such genes is the RBTN family located on chromosomes 11 and 12. Two members of this family, RBTN1/Ttg-1 and RBTN2/Ttg-2, are located near recurring T cell acute lymphocytic leukaemia-associated translocations. Chromosomal translocations to both RBTN1/Ttg-1 and RBTN2/Ttg-2 involve T cell receptor (TCR) genes as result of an erroneous V(D)J joining process. RBTN1/Ttg-1 and RBTN2/Ttg-2 encode related proteins consisting of two cysteine-rich regions called LIM domains. The fact that LIM domains can be found with or without associated homeodomain led to the suggestion that the LIM domains may function as regulators of transcription, and that alterations of transcription networks, after chromosomal translocations, lead to leukaemia. This is a common feature that has been noted in the activation of transcription factors with a variety of structural motifs that include the basic helix-loop-helix motif and the homeodomain in leukaemias.
Sánchez-García
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MRC Laboratory of Molecular Biology, Cambridge, UK.
Rabbitts
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D004254:DNA Nucleotidyltransferases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic; D006128:Growth / Q000235:genetics*; D006801:Humans; D007448:Invertebrates / Q000235:genetics; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008667:Metalloproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014157:Transcription Factors; D014178:Translocation, Genetic; D045567:VDJ Recombinases; D016335:Zinc Fingers / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C065072:LMO1 protein, human; C085117:LMO2 protein, human; C513044:Lmo1 protein, mouse; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases