Induction of the growth inhibitor IGF-binding protein 3 by p53.
Transcriptional activation of target genes represents an important component of the tumour-suppressor function of p53 and provides a functional link between p53 and various growth-regulatory processes, including cell cycle progression (p21/WAF1), DNA repair (GADD45) and apoptosis (bax). Here we use a differential cloning approach to identify the gene encoding insulin-like growth factor binding protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3 gene expression by wild-type but not mutant p53 is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may link p53 to potential novel autocrine/paracrine signalling pathways and to processes regulated by or dependent on IGF(s), such as cellular growth, transformation and survival.
Buckbinder
L
L
Department of Molecular Genetics, Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, New Jersey 08543-4000, USA.
Talbott
R
R
Velasco-Miguel
S
S
Takenaka
I
I
Faha
B
B
Seizinger
B R
BR
Kley
N
N
D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays
D006131:Growth Inhibitors; D018972:Insulin-Like Growth Factor Binding Protein 3; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin; D004247:DNA