High-mobility-group chromosomal proteins, HMGA1 as potential tumour markers

The high-mobility-group, HMGA1 (formerly HMG I/Y) family of non-histone, chromosomal proteins consisting of HMGA1a, HMGA1b and HMGA2 are known as 'architectural transcription factors' because of their specific protein-protein and protein-DNA interactions. In the recent past, the HMGA1 family has got special attention and has been given several names like 'oncoproteins', 'enhancers', 'multifunctional proteins', 'architectural elements', 'tumour markers', etc. The increased interest in the last few years in these small molecular weight proteins is due to their high expression in neoplastic transformation of cells and metastatic tumour progression. Because of their elevated levels found in a wide variety of human cancers, they are suggested as novel diagnostic tumour markers. These proteins have three conserved binding domains called 'AT-hooks' which bind to the narrow minor groove of the DNA in the AT-rich sequences and bring conformational changes in DNA and chromatin. They are also known to participate in protein-protein interaction in the organization of transcriptional complex and assembly of 'enhanceosome'. Since HMGA1 proteins are the only oncoproteins known so far, which bind to the DNA minor groove, they are also used as potential targets for anti-tumour drugs.