Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 43, Pages 33607-33613Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M002547200
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- NIAID NIH HHS [1RO1 AI40203] Funding Source: Medline
- NIDDK NIH HHS [2R01 DK47591] Funding Source: Medline
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Insulin-like growth factor-binding protein (IGFBP)-3 regulates apoptosis in an IGF-independent fashion and has been shown to localize to nuclei. We cloned the nuclear receptor retinoid X receptor-alpha>(*) over bar * (RXR-alpha) as an IGFBP-3 protein partner in a yeast two-hybrid screen. Multiple methodologies showed that IGFBP-3 and RXR-alpha bind each other within the nucleus. IGFBP-3-induced apoptosis was abolished in RXR-alpha -knockout cells. IGFBP-3 and RXR ligands mere additive in inducing apoptosis in prostate cancer cells. IGFBP-3 enhanced RXR response element and inhibited RARE signaling. Thus, RXR-alpha -IGFBP-3 interaction leads to modulation of the transcriptional activity of RXR-alpha and is essential for mediating the effects of IGFBP-3 on apoptosis.
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