The sterol-sensing domain (SSD) is a ∼180 amino acid long region that is conserved in six families of proteins such as hydroxymethylglutaryl-CoA reductase (HMDH), SREBP (sterol regulatory element binding protein) cleavage activating protein (SCAP), Niemann-Pick C-1 type protein (NPC1), Patched, Patched-related and Dispatched [1]. This domain encompasses five transmembrane helices and is involve...

The Hedgehog (HH) signaling proteins control cell fates and patterning during animal development. In Drosophila, HH protein induces the transcription of target genes encoding secondary signals such as DPP and WG proteins by opposing a repressor system. The repressors include Costal2, protein kinase A, and the HH receptor Patched. Like HH, the kinase Fused and the transcription factor Cubitus in...

Hedgehog ligands control tissue development and homeostasis by alleviating repression of Smoothened, a seven-pass transmembrane protein. The Hedgehog receptor, Patched, is thought to regulate the availability of small lipophilic Smoothened repressors whose identity is unknown. Lipoproteins contain lipids required to repress Smoothened signaling in vivo. Here, using biochemical fractionation and...

The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes in development, but the nature of these changes is largely unknown. In butterflies, eyespots have evolved as new pattern elements that develop from special organizers called foci. Formation of these foci is associated with novel expression patterns of the Hedgehog signa...

SHH, IHH, and DHH are lipid-modified secreted proteins binding to Patched receptors, and CDON, BOC or GAS1 co-receptors. In the absence of Hedgehog signaling, GLI1 is transcriptionally repressed, GLI2 is phosphorylated by GSK3 and CK1 for the FBXW11 (betaTRCP2)-mediated degradation, and GLI3 is processed to a cleaved repressor. In the presence of Hedgehog signaling, Smoothened is relieved from ...

A novel model, called evolutionary patched model, based on the patched conic approximation is applied to the optimization of space missions with engineering constraints in this paper. The interplanetary trajectory consists of geocentric escape orbit, heliocentric transfer orbit and target capture orbit. The model, firstly, gets the escape orbit and capture orbit by optimizing the elements of or...

Intercellular signaling is crucial for embryonic patterning, cell specification and tissue induction. Hedgehog (Hh) encodes a secreted signal originally identified in Drosophila (Nüsslein-Volhard and Wieschaus, 1980). Vertebrate family members have been subsequently isolated (Echelard et al., 1993; Ekker et al., 1995; Krauss et al., 1993; Riddle et al., 1993; Roelink et al., 1994). In vivo and ...

Glypican-3 (GPC3) is a heparan sulfate (HS) proteoglycan that is bound to the cell membrane through a glycosylphosphatidylinositol link. This glypican regulates embryonic growth by inhibiting the hedgehog (Hh) signaling pathway. GPC3 binds Hh and competes with Patched (Ptc), the Hh receptor, for Hh binding. The interaction of Hh with GPC3 triggers the endocytosis and degradation of the GPC3-Hh ...

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety of other tumors, and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial and sporadic BCCs display loss of heterozygosity in this region, consistent with the gene being a tumor suppre...