Regulation of somatic growth by the p160 coactivator p/CIP.
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.
Wang
Z
Z
Howard Hughes Medical Institute and Department of Biology, University of California, School of Medicine at San Diego, La Jolla, CA 92093, USA.
Rose
D W
DW
Hermanson
O
O
Liu
F
F
Herman
T
T
Wu
W
W
Szeto
D
D
Gleiberman
A
A
Krones
A
A
Pratt
K
K
Rosenfeld
R
R
Glass
C K
CK
Rosenfeld
M G
MG
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D015534:Trans-Activators