The Hedgehog (Hh) signaling pathway has conserved roles in development of species ranging from Drosophila to humans. Human supressor of fused HSu(Fu) acts as a negative regulator in the hedgehog signaling (SHH) pathway by down-regulating GLI1-mediated transactivation of target genes (1). HSu(fu) was found to repress activity of the zinc-finger transcription factor Gli, which mediates Hedgehog signaling in vertebrates, and to physically interact with Gli, Gli2 and Gli3 (2). The sonic hedgehog signaling pathway directs the embryonic development of diverse organisms and is disrupted in a variety of malignancies. Several of mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism (3).
