A transcriptional partner for MAD proteins in TGF-β signalling

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Abstract
The transforming-growth-factor-β (TGF-β) superfamily is critical for establishing mesoderm during early embryogenesis in Xenopus. The transcriptional activation of Mix.2, an immediate-early response gene specific to activin-like members of the TGF-β superfamily, is associated with the rapid appearance of a site-specific DMA-binding activity that recognizes a fifty-base-pair regulatory element known as ARE in the Mix.2 promoter. Cloning of the site-specific DNA-binding component of this activity revealed it to be a new winged-helix transcription factor and a direct target for signalling by the TGF-β superfamily. XMAD2, a recently identified TGF-β signal transducer, forms a complex with the transcription factor in an activin-dependent fashion to generate an activated ARE-binding complex. A model is proposed to explain how TGF-β superfamily signals might regulate the expression of specific genes in the early embryo.