Model for the switching of the dual function of Rdx depending on Hh signal strength.

In region 1 abutting the A/P boundary, which receives strong Hh signal, the Rdx levels are high. In this region, Rdx inhibits the nuclear import of Ci-155 by competing with importin α3 for binding to Ci-155 at the nuclear pore complex. This maintains the nuclear Ci-155 at low levels. Low levels of nuclear Ci-155 selectively activate the transcription of kn. Low levels of nuclear Ci-155 may be central to the selective induction of specific Hh target genes, such as kn. On the other hand, in region 2 distant from the A/P boundary, which exhibits moderate levels of Hh signal, the Rdx levels are moderate. In this region, the nuclear import of Ci-155 is allowded, which maintains the nuclear Ci-155 at relatively high levels; however, the nuclear Ci-155 level is negatively regulated by Rdx via a proteasome-dependent degradation. The relationship between Hh signal, Rdx and Ci is shown below. Strong Hh signal induces Rdx expression, which inhibits the nuclear entry of Ci-155.