The high mobility group protein, HMGI-C

HMGI-C is a nuclear phosphoprotein that contains three short DNA-binding domains (AT-hooks) and a highly acidic C-terminus. Interest in the protein has recently been stimulated by three observations: the expression of the gene is cell-cycle regulated, the gene is rearranged in a number of tumours of mesenchymal origin and mice that have both HMGI-C alleles disrupted exhibit the pygmy phenotype. These observations suggest a role for HMGI-C in cell growth, more specifically, during foetal growth since the protein is normally only expressed in embryonic tissues. It is likely that the HMGI-C protein acts as an architectural transcription factor, regulating the expression of one or more genes that control embryonic cell growth. Since HMGI-C binds to the minor groove of AT-rich DNA this interaction could be a target for minor groove chemotherapeutic agents in the treatment of sarcomas expressing the rearranged gene.