Methods and Means for Controlling the Endocytosis and Subsequent Degradation of a Cell Surface Protein

A method for increasing the presence of a receptor at the surface of a cell, the method comprising providing to said cell an inhibitor that at least in part is capable of inhibiting the interaction of an F-box protein with a ubiquitin/proteasome binding site of said receptor, wherein said ubiquitin/proteasome binding site comprises the amino acid sequence motif xDSWxEFIxxD or a sequence essentially corresponding thereto.

A method for controlling the presence of a growth hormone receptor (GHR) at the surface of a cell, the method comprising interfering with the interaction of an F-box protein with a ubiquitin/proteasome binding site of said GHR.

A method for increasing the presence of a GHR at the surface of a cell, the method comprising providing to said cell an inhibitor that at least in part is capable of inhibiting the interaction of an F-box protein with a ubiquitin/proteasome binding site of said GHR.

A method for selecting an inhibitor capable of inhibiting the interaction of an F-box protein with a ubiquitin/proteasome binding site, the method comprising the steps of

• contacting, in the absence or presence of a possible inhibitor, said F-box protein or a functional part and/or equivalent thereof with a first labeled compound comprising at least a proteinaceous part comprising the amino acid sequence xDSWxEFIxxD or a sequence essentially corresponding thereto and
• determining the amount of said first labeled compound bound to said F-box protein in the presence or absence of said inhibitor and comparing the obtained amounts
• selecting the inhibitor that results in a decreased amount of said bound first labeled compound.