Functional diversity of LIM proteins: amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2.
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.
Sánchez-García
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MRC Laboratory of Molecular Biology, Cambridge, UK.
Axelson
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Rabbitts
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TH
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012441:Saccharomyces cerevisiae; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C065072:LMO1 protein, human; C085117:LMO2 protein, human; D008667:Metalloproteins; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors