Nuclear effects: unexpected intracellular actions of insulin-like growth factor binding protein-3

in Journal of Endocrinology
Authors:
KW Lee
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and
P Cohen
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DOI:
https://doi.org/10.1677/joe.0.1750033
Volume/Issue:
Volume 175: Issue 1
Article Type:
Other
Page Range:
33–40
Online Publication Date:
01 Oct 2002
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Insulin-like growth factor (IGF) binding protein (IGFBP)-3 has been shown to be a growth inhibitory, apoptosis-inducing molecule by virtue of its ability to bind IGFs, in addition to previously demonstrated IGF-independent effects. The recent discovery of the interaction between nuclear IGFBP-3 and 9-cis retinoic acid receptor-alpha (retinoid X receptor alpha RXRalpha), a nuclear receptor, and its involvement in the regulation of transcriptional signaling and apoptosis represents an important paradigm shift in the understanding of IGFBP function. RXRalpha is required for the apoptosis-inducing effects of IGFBP-3. IGFBP-3 and RXR ligands are additive in inducing apoptosis in cancer cells. IGFBP-3 has direct effects on gene transcription, as RXR response element reporter signaling was enhanced and the all-trans retinoic acid receptor response element reporter signaling was inhibited. Accumulating evidence further confirms IGF-independent functions of this multifunction binding protein. Other binding proteins, in addition to other members of the IGF axis, have now been described in the nucleus and are postulated to have effects on transcriptional events. Investigation into these new interactions will expose new protein partners in the interface between the nuclear receptor and growth factor pathways and reveal new targets to be exploited in the treatment of cancer and other diseases.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Page(s):
8
Article Type:
Other
Print Publication Date:
01 Oct 2002
Online Publication Date:
01 Oct 2002