Disease relevance of UNC5B

• We show here that the expression of the human UNC5A, UNC5B, or UNC5C is down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers [1].

High impact information on UNC5B

• The p53RDL1 gene product contains a cytoplasmic carboxy-terminal death domain that is highly homologous to rat Unc5H2, a dependence receptor involved in the regulation of apoptosis, as well as in axon guidance and migration of neural cells [2].
• Conversely, when p53RDL1 interacted with its ligand, Netrin-1, p53-dependent apoptosis was blocked [2].
• Here, we show that UNC5H2 physically interacts with the serine/threonine kinase death-associated protein kinase (DAP-kinase) both in cell culture and in embryonic mouse brains [3].
• The lossreduction of expression may be a crucial mechanism for tumorigenicity because the expression of UNC5H1, UNC5H2, or UNC5H3 inhibits tumor cell anchorage-independent growth and invasion [1].
• The antimelanoma effect of IFN-gamma was also associated with the up-regulation of the proapoptotic dependence receptor UNC5H2 and the Wnt inhibitor Dkk-1 [4].

Biological context of UNC5B

• In the absence of netrin-1, UNC5B mediates p53-dependent apoptosis [5].
• The expression of UNC5H2 in the brain and immune system suggests that this novel inhibitor of G protein signaling may have broad significance for axonal guidance and chemotaxis [6].

Associations of UNC5B with chemical compounds

• In particular, Semaphorin3E and its receptor plexinD1 in addition to the Netrin receptor UNC5B have recently been shown to direct endothelial tip cell navigation [7].

Regulatory relationships of UNC5B

• UNC5H2-induced apoptosis depends on the interaction of the death domain at the C-terminus with the DAP-kinase death domain and caspase cleavage near the transmembrane region [8].

References