Regulation of somatic growth by the p160 coactivator p/CIP

A family of p160 coactivators was initially identified based on ligand-depe ndent interactions with nuclear receptors and thought to function, in part, by recruiting CREB-binding protein/p300 to several classes of transcriptio n factors. One of the p160 factors, p/CIP/AIB1,often amplified and overexpr essed in breast cancer, also exhibits particularly strong interaction with CREB-binding protein/p300. In this manuscript, we report that p/CIP, which exhibits regulated transfer from cytoplasm to nucleus, is required for norm al somatic growth from embryonic day 13.5 through maturity. Our data sugges t that a short stature phenotype of p/CIP gene-deleted mice reflect both al tered regulation of insulin-like growth factor-1 (IGF-1)gene expression in specific tissues and a cell-autonomous defect of response to IGF-1, includi ng ineffective transcriptional activities by several classes of regulated t ranscription factors under specific conditions. The actions of p/CIP are th erefore required for full expression of a subset of genes critical for regu lating physiological patterns of somatic growth in mammals.