Two MAD tails: what the recent knockouts of Mad1 and Mxi1 tell us about the MYC/MAX/MAD network.

Members of the MAD/MXI protein family heterodimerize with MAX and repress transcription by recruiting a chromatin-modifying co-repressor complex to specific DNA target genes. Repression mediated by MAD is thought to antagonize the transcriptional activation and proliferation-promoting functions of MYC-MAX heterodimers. Because they are induced during differentiation, it has been suggested that MAD proteins act to limit cell proliferation during terminal differentiation. There is also controversial evidence that these proteins may function as tumor suppressors. Recently, targeted gene deletions of two members of this gene family, Mad1 and Mxi1, have been carried out in mice. Although these animals display what appear to be quite different phenotypes, further analysis supports the view that both these proteins function in cell-cycle exit during terminal differentiation, and that at least MXI1 can act as a tumor suppressor.