Transcription Nuclear Export Escort for RXR

The retinoid X receptor (RXR) is a nuclear hormone receptor that heterodimerizes with other nuclear receptors to regulate transcription. Hence, localization to the nucleus is critical for its function. Katagiri et al. report that NGFI-B, another nuclear receptor that heterodimerizes with RXR, causes the nuclear export of RXR in response to nerve growth factor (NGF). By following the movement of proteins labeled with green fluorescent protein (GFP), the export of GFP-RXR accompanies the export of GFP-NGFI-B in response to NGF treatment of transfected cells. When a putative nuclear export signal is mutated in NGFI-B, this response is inhibited. Mutational analysis also indicates that a serine residue in the amino terminus of NGFI-B is critical to the export of both proteins, and the authors propose that phosphorylation of this residue controls nuclear export. The presence of NGFI-B interfered with the DNA-binding activity of a heterodimer comprised of RXR and the retinoic acid receptor, and treatment of cells with NGF also decreased retinoic acid-induced transcription. Thus, RXR activity may be regulated in part by the movement of NGFI-B, and the association of these nuclear receptors may constitute a point of cross talk between the NGF and retinoic acid signaling pathways.

Katagiri, Y., Takeda, K., Yu, Z.-X., Ferrans, V.J., Ozato, K., and Guroff, G. (2000) Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B. Nature Cell Biol. 2: 435-440. [Online Journal]