The present invention relates to the identification of a PEST motif in Suppressor of Cytokine Signalling (SOCS) proteins, the deletion/inactivation of which has been found to increase the stability of the protein whilst maintaining at least one biological activity of the protein. Such SOCS proteins with deleted/inactivated PEST motifs can be used in gene and protein therapy procedures to provide a more stable SOCS protein when compared to the native protein. The present invention also relates to the characterization of the structure of SOCS proteins, and methods of using this structural information to identify compounds which modulate the activity of SOCS.