Distinct repressive properties of the mammalian and fish orphan nuclear receptors SHP and DAX-1

作者：Park Yun Yong; Teyssier Catherine; Vanacker Jean Marc; Choi Hueng Sik^*

来源：Molecules and Cells, 2007, 23(3): 331-339.

• DAX-1
• fish
• mammals
• nile Tilapia transcriptional repression
• orphan nuclear receptor
• SHP

It has been suggested that the structure and function of nuclear receptors are evolutionally conserved. Here, we compare the molecular functions of the nile tilapia (Oreochromis niloticus) small heterodimer partner (nSHP/NR0B2) and the Dosage-sensitive sex reversal AHC critical region on X chromosome gene 1(nDAX-I/NR0B1) with those of human SHP and DAX-1 (hSHP and hDAX-1, respectively). We found that, upon transient cotransfection of human cells, nDAX-1 repressed the activity of tilapia SF-1 (nSF-1) but not that of human SF-1 although the physical interaction with human SF-1was retained. Similarly, nSHP repressed the activity of nSF-1, whereas hSHP did not, pointing to divergent evolution of SHP/SF-1 in fish and human. We thus propose that the repressive functions of SHP and DAX-1 have been conserved in fish and mammals although with different transcriptional targets and mechanisms. These differences provide new insights into the physiological diversification of atypical orphan nuclear receptors during vertebrate evolution.

• 出版日期2007-6-30