THE MADS-BOX FAMILY OF TRANSCRIPTION FACTORS

The MADS-box family of transcription factors has been defined on the b asis of primary sequence similarity amongst numerous proteins from a d iverse range of eukaryotic organisms including yeasts, plants, insects , amphibians and mammals. The MADS-box is a conserved motif found with in the DNA-binding domains of these proteins and the name refers to fo ur of the originally identified members: MCM1 AG, DEFA and SRF. Severa l proteins within this family have significant biological roles. For e xample, the human serum-response factor (SRF) is involved in co-ordina ting transcription of the protooncogene c-fos,whilst MCM1 is central t o the transcriptional control of cell-type specific genes and the pher omone response in the yeast Saccharomyces cerevisiae. The RSRF/MEF2 pr oteins comprise a subfamily of this class of transcription factors whi ch are key components in muscle-specific gene regulation. Moreover, in plants, MADS-box proteins such as AG, DEFA and GLO play fundamental r oles during flower development. The MADS-box is a contiguous conserved sequence of 56 amino acids, of which 9 are identical in all family me mbers described so far. Several members have been shown to form dimers and consequently two functional regions within the MADS-box have been defined. The N-terminal half is the major determinant of DNA-binding specificity whilst the C terminal half is necessary for dimerisation. This organisation allows the potential formation of numerous proteins, with subtly different DNA-binding specificities, from a limited numbe r of genes by heterodimerisation between different MADS-box proteins. The majority of MADS-box proteins bind similar sites based on the cons ensus sequence CC(A/T)(6)GG although each protein apparently possesses a distinct binding specificity. Moreover, several MADS-box proteins s pecifically recruit other transcription factors into multi-component r egulatory complexes. Such interactions with other proteins appears to be a common theme within this family and play a pivotal role in the re gulation of target genes.