Recombinant Human DAN Fc Chimera Protein, CF

DAN (differential screening-selected gene aberrative in neuroblastoma) was initially identified as a gene whose expression is downregulated in src-transformed rat fibroblasts. Human DAN was isolated from a normal lung cDNA library using mouse DAN as a probe. DAN has now been shown to be a prototypical member of the DAN family of secreted glycoproteins that are putative antagonists for TGF-beta superfamily proteins. DAN family members share a cysteine-rich domain that is structurally related to the cysteine-knot motif found in TGF-beta superfamily ligands. There are at least five mammalian DAN family members including DAN, Gremlin/DRM, Cer1 (Cerberus-related), Dante and PRDC (protein related to DAN and cereberus). Additional DAN family members include Xenopus Cerberus, chick Caronte and C. elegans CeCan 1. The DAN family of proteins are thought to act as antagonists by binding TGF-beta family ligands and preventing their interactions with signaling receptor complexes. Recombinant human DAN preparations from R&D Systems have been shown to bind BMP-4 in a functional ELISA and to inhibit BMP-4 mediated bioactivity in ATDC 5 chrondrogenic cells. It is likely the various DAN family members and other TGF-beta BMP antagonists including Noggin, Chordin, Follistatin and TSG can selectively antagonize the activities of different subsets of TGF-beta superfamily ligands. These antagonists represent one of the many elaborate regulatory mechanisms that have evolved to control the bioactivities of the TGF-beta superfamily ligands.