A bidirectional regulation between the TR2/TR4 orphan receptors (TR2/TR4) and the ciliary neurotrophic factor (CNTF) signaling pathway.
Previously, we reported that the nuclear orphan receptor TR4 could induce transcriptional activity via the 5th intron of the ciliary neurotrophic factor (CNTF) alpha receptor gene (CNTFR-I5). Here we show CNTF could increase TR4 expression and enhance the DNA-binding capacity of TR4. Interestingly, the expression of TR2, a close family member of TR4, could also be induced by CNTF. In return, TR2 induced CNTFRalpha transcriptional activity through binding to a direct repeat response element of AGGTCA within CNTFR-I5. The possibility of this mutual influence between TR2 and the CNTF signaling was further strengthened by in situ hybridization. Similar expression patterns of TR2 and CNTFRalpha were observed in most of the developing neural structures such as the ganglia, neural epithelia, spinal cord, and the periventricular areas of brain. Together, our data suggest that an interaction between TR2/TR4 and the CNTF signaling pathway may occur, supporting the hypothesis that TR2/TR4 may play important roles in neurogenesis.
George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Biochemistry, University of Rochester Medical Center, Rochester, New York 14642, USA.
W J
WJ
Young
Y F
YF
Lee
S M
SM
Smith
C
C
Chang
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor; D018076:DNA, Complementary; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D011485:Protein Binding; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
D020934:Ciliary Neurotrophic Factor; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C539823:Nr2c1 protein, mouse; C490514:Nr2c2 protein, mouse; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone