SUPPRESSOR OF FUSED LINKS FUSED AND CUBITUS-INTERRUPTUS ON THE HEDGEHOG SIGNALING PATHWAY

The Hedgehog (Hh) family of signalling proteins [1] mediate inductive interactions either directly or by controlling the transcription of ot her secreted proteins through the action of Gli transcription factors, such as Cubitus interruptus (Ci) [2]. In Drosophila, the transcriptio n of Hh targets requires the activation of the protein kinase Fused (F u) and the inactivation of both Suppressor of fused (Su(fu)) and Costa l-2 (Cos-2) [3]. Fu is required for Hh signalling in the embryo and in the wing imaginal disc and acts also as an antitumorigen in ovaries [ 4]. All fu-phenotypes are suppressed by the loss of function of Su(fu) [5]. Fu, Cos-2 and Ci are coassociated in vivo in large complexes tha t are bound to microtubules in a Hh-dependent manner [6,7]. Here we in vestigate the role of Su(fu) in the intracellular part of the Hh signa lling pathway. Using the yeast two-hybrid method and an in vitro bindi ng assay, we show that Su(fu), Ci and Fu can interact directly to form a trimolecular complex, with Su(fu) binding to both its partners simu ltaneously. Su(fu) and Ci also coimmunoprecipitate from embryo extract s. Mle propose that, in the absence of Hh signalling, Su(fu) inhibits Ci by binding to it and that, upon reception of the Hh signal, Fu is a ctivated and counteracts Su(fu), leading to the activation of Ci. (C) Current Biology Ltd ISSN 0960-9822.