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 inv olving chromosome 11 in some T cell acute leukaemias. The RBTN protein s belong to the LIM family which comprises proteins with one, two or t hree cysteine-rich LIM domains, sometimes together with homeodomains o r protein kinase domains. The RBTN1 and RBTN2 proteins comprise only t andem LIM domains. We report that RBTN1 and RBTN2 proteins are capable of supporting transcriptional transactivation of specific reporter ge nes in transfection assays. The results, using intact proteins or fusi ons with the homeodomain of the heterologous protein Isl-1, show that this transcriptional activation ability resides in the NH2-terminal pa rts of both proteins. The use of yeast assays with RBTN2 shows that RB TN2 forms homodimers and that the NH2-terminal 27 amino acids are suff icient to facilitate transcriptional transactivation. These data expan d the functional diversity of the LIM-domain protein family and they a ugment the previously defined relationship between chromosomal translo cations and transcriptional activation.