Rhomboid Family, Member 2 (RHBDF2)

RHBDF2 was shown to be up regulated in tumors and silencing of RHBDF2 inhibited TNFα response, scratch wound closure and tube formation. In zebrafish RHBDF2 was shown to be expressed, although not exclusively, in endothelial cells. RHBDF2 morpholinos inhibited intersomitic vessel formation and showed aberrant arteriogenesis, whereas no effects were observed in the venous system. CLEC14A forms a complex with RHBDL2 and is subsequently cleaved by RHBDL2 in the transmembrane region, resulting in inactivation of the protein. RHBDL2 itself is regulated by RHBDF2, which specifically associates with RHBDL2 to inhibit its activity. In conclusion, Bicknell identified a new signaling pathway in which RHBDF2, RHBDL2 and CLEC14A regulate tumor angiogenesis.