Regulation of somatic growth by the p160 coactivator p/CIP.

Abstract

A family of p160 coactivators was initially identified based on ligand-dependent interactions with nuclear receptors and thought to function, in part, by recruiting CREB-binding protein/p300 to several classes of transcription factors. One of the p160 factors, p/CIP/AIB1, often amplified and overexpressed 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 normal somatic growth from embryonic day 13.5 through maturity. Our data suggest that a short stature phenotype of p/CIP gene-deleted mice reflect both altered regulation of insulin-like growth factor-1 (IGF-1) gene expression in specific tissues and a cell-autonomous defect of response to IGF-1, including ineffective transcriptional activities by several classes of regulated transcription factors under specific conditions. The actions of p/CIP are therefore required for full expression of a subset of genes critical for regulating physiological patterns of somatic growth in mammals.

• Authors: Z Wang, D W Rose, O Hermanson, F Liu, T Herman, W Wu, D Szeto, A Gleiberman, A Krones, K Pratt, R Rosenfeld, C K Glass, M G Rosenfeld
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 25 Pg. 13549-54 (Dec 05 2000) ISSN: 0027-8424 [Print] United States
• PMID: 11087842 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA Primers
• Trans-Activators

Topics

• Animals
• Base Sequence
• Cell Division (physiology)
• Cells, Cultured
• DNA Primers
• Female
• Gene Deletion
• Mice
• Mice, Inbred C57BL
• Trans-Activators (genetics, physiology)