The Dan (Differential screening-selected gene aberrative in neuroblastoma; also known as N03) gene was first identified as the putative rat tumor suppressor gene and encodes a protein structurally related to Cerberus and Gremlin in vertebrates. It is a founding member of the DAN family of secreted proteins; acts as an inhibitor of cell cycle progression and is closely involved in retinoic acid-induced neuroblastoma differentiation. There are at least five mammalian protein members in the evolutionarily conserved Dan family including DAN; Gremlin/DRM; Cer1 (Cerberus-related); Dante and PRDC (protein related to DAN and cereberus); and share the C-terminal cystine-knot motif. As a secreted glycoprotein; DAN is a member of a class of glycoproteins shown to be secreted inhibitors of the transforming growth factor-beta (TGF-beta) and bone morphogenic protein pathways. It binds to BMPs and preventing their interactions with signaling receptor complexes; and accordingly regulates the processes of embryonic development and tissue differentiation. DAN gene product may have an important role in regulation of the entry of cells into the S phase. In addition; DAN gene product possesses an ability to revert phenotypes of transformed rat fibroblasts and represents a candidate tumour suppressor gene for neuroblastoma.
The Dan (Differential screening-selected gene aberrative in neuroblastoma , also known as N03) gene was first identified as the putative rat tumor suppressor gene and encodes a protein structurally related to Cerberus and Gremlin in the vertebrates. It is a founding member of the DAN family of secreted proteins , acts as an inhibitor of cell cycle progression , and is closely involved in retinoic acid-induced neuroblastoma differentiation. There are at least five mammalian protein members in the evolutionarily conserved Dan family including DAN , Gremlin/DRM , Cer1 (Cerberus-related) , Dante , and PRDC (protein related to DAN and Cerberus) , and share the C-terminal cystine-knot motif. As a secreted glycoprotein , DAN is a member of a class of glycoproteins shown to be secreted inhibitors of the transforming growth factor-beta (TGF-beta) and bone morphogenic protein pathways. It binds to BMPs and preventing their interactions with signaling receptor complexes , and accordingly regulates the processes of embryonic development and tissue differentiation. DAN gene product may have an important role in the regulation of the entry of cells into the S phase. Besides , the DAN gene product possesses an ability to revert phenotypes of transformed rat fibroblasts and represents a candidate tumor suppressor gene for neuroblastoma.
NCAM1, also known as CD56, is a neural adhesion protein (NCAM) which belongs to the immunoglobulin superfamily. NCAM is involved in neural development and in plasticity in the adult brain. UCHL1 is a novel interaction partner of both NCAM isoforms that regulates their ubiquitination and intracellular trafficking. NCAM1 is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. NCAM1 has also been shown to be involved in the expansion of T cells and dendritic cells which play an important role in immune surveillance.
Neural cell adhesion molecule 1 (NCAM-1) is a single-pass type I membrane protein, it belongs to a family of membrane-bound glycoproteins that are involved in Ca2+ independent cell matrix and homophilic or heterophilic cell-cell interactions. NCAM-1 is synthesized as a 761 aa preproprecursor that contains a 19 aa signal sequence, a 722 aa GPI-linked mature region, and a 20 aa C-terminal prosegment. The molecule contains five C-2 type Ig-like domains and two fibronectin type-III domains. NCAM-1 is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. Acting as a receptor for rabies virus, NCAM-1 in the adult brain shows a decline of sialylation relative to earlier developmental periods.
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