Two MAD tails: what the recent knockouts of Madl and Mxil tell us about the MYC/MAX/MAD network

Members of the MAD/MXI protein family heterodimerize with MAX and repress t ranscription by recruiting a chromatin-modifying co-repressor complex to sp ecific DNA target genes. Repression mediated by MAD is thought to antagoniz e the transcriptional activation and proliferation-promoting functions of M YC-MAX heterodimers. Because they are induced during differentiation, it ha s been suggested that MAD proteins act to limit cell proliferation during t erminal differentiation. There is also controversial evidence that these pr oteins may function as tumor suppressors. Recently, targeted gene deletions of two members of this gene family, Mad1 and Mxi1, have been carried out i n mice. Although these animals display what appear to be quite different ph enotypes, further analysis supports the view that both these proteins funct ion in cell-cycle exit during terminal differentiation, and that at least M XI1 can act as a tumor suppressor. (C) 1999 Elsevier Science B.V. All right s reserved.