Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1: a candidate for displacement by LMO proteins in T cell acute leukaemia.
The T cell oncogenes LMO1 and LMO2 are activated by distinct chromosomal translocations in childhood T cell acute leukaemias. Transgenic mouse models of this disease demonstrate that enforced expression of Lmo1 and Lmo2 cause T cell leukaemias with long latency and that Lmo2 expression leads to an inhibition of the T cell differentiation programme, prior to overt disease. These functions appear to be partly mediated by interaction of LMO1 or LMO2 with the LIM-binding protein LDB1/ NLI1. We have now identified a new member of the Lmo family, designated Lmo4, via its interaction with Ldb1. Lmo4 is widely expressed in mouse tissues, including adult thymus (mainly CD4, CD8-double positive T cells) and embryonic thymus (mainly CD4, CD8-double negative T cells). These characteristics imply that Ldb1-Lmo4 interaction may function in the T cell developmental programme and that enforced expression of LMO1 or LMO2 by chromosomal translocations or transgenesis may displace Lmo4 from this complex and thereby influence T cell differentiation prior to T cell tumour occurrence.
Grutz
G
G
MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK.
Forster
A
A
Rabbitts
T H
TH
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008667:Metalloproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D009928:Organ Specificity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486312:LDB1 protein, human; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; C513044:Lmo1 protein, mouse; C513188:Lmo2 protein, mouse; C491976:Lmo4 protein, mouse; D008667:Metalloproteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors