GERM-CELL NUCLEAR FACTOR - AN ORPHAN RECEPTOR WITH UNEXPECTED PROPERTIES

The orphan receptor germ cell nuclear factor (GCNF) is a member of the superfamily of nuclear receptors. During embryogenesis GCNF expressio n is restricted to the developing nervous system, whereas in the adult the receptor is also expressed during specific stages in maturing ger m cells of the ovary and testis. Therefore GCNF may participate in the regulation of neurogenesis and reproductive functions. Binding of GCN F to the consensus element TCA[AG(G/T)TCA](2) (conRE), to the direct r epeat DNA element AGGTCAAGGTCA (DR0), and to extended half-sites such as TCAAGGTCA (XRE) has been demonstrated, but no natural GCNF target g ene has been identified. However, due to an overlapping temporal expre ssion pattern and the presence of DR0-type elements in their promoter regions, the protamine 1 and 2 genes have been proposed as potential c andidates for a regulation by GCNF. Sines GCNF binds as a homodimer to all three elements (conRE, DR0, and XRE) the receptor exhibits an exc eptional property within the nuclear receptor superfamily. Homodimeric binding of GCNF to extended half-sites requires the presence of a nov el demerization motif located in the putative helix 3 of the GCNF liga nd-binding domain (LBD). Since neither potential ligands nor heterodim erization partners or cofactors for GCNF have been identified, little is known about the mechanisms by which the receptor controls transcrip tional processes. Due to the lack of a conserved transcriptional activ ation function 2 core motif (AF-2 AD core) in the helix 12 region of t he GCNF LED, it has been suggested that GCNF functions as a repressor of transcription. In addition, recent data suggest that the helix 12 r egion displays functions distinct from those in other nuclear receptor s and is involved in the control of DNA binding. Together, these repor ts indicate that GCNF exhibits novel properties distinct from other me mbers of the nuclear receptor superfamily.