PROBLEM TO BE SOLVED: To provide a new ubiquitin ligase and its adapter components, as well as applications thereof.SOLUTION: The invention provides a ubiquitin ligase controlling agent containing a ubiquitin ligase component consisting of BTBD3 (BTB(POZ) Domain Containing 3), SPOP (Speckle type POZ protein), or a derivative thereof, a ubiquitin ligase component consisting of the same and CUL3 (Cullin 3) or a derivative thereof, a ubiquitin ligase comprising the component concerned, and a substance which controls the expression of BTBD3 or SPOP. The invention also provides a ubiquitin ligase controlling agent comprising a substance which controls the binding to CUL3 of BTBD3 or SPOP, or a VEGFR2 signal regulatory agent, an angiogenesis regulatory agent, or a preventive or therapeutic agent of the diseases caused by the defect of VEGFR2 signalling system containing any one of the components, ubiquitin ligase and controlling agents.
