The suppressors of cytokine signalling E3 ligases behave as tumour suppressors

Many studies have suggested that E3 ubiquitin ligases can behave as either oncogenes or tumour suppressor genes and, recently, it has become clear that the SOCS (suppressor of cytokine signalling) E3 ligases fit this mould. While most cancer-associated E3s regulate the cell cycle or DNA repair, the SOCS proteins inhibit growth factor responses by degrading signalling intermediates such as JAKs (Janus kinases) via the SOCS-box-associated ECS (Elongin–Cullin–SOCS) E3 ligase. Clinical studies have found that (epi)genetic (mutation or methylation) phenomena can occur in many solid tumours and a growing number of clinical findings reveal post-translational modifications that disrupt SOCS function in haematological malignancy. In the present review, we provide a summary of the functions of the SOCS E3s and propose the potential use of members of this family as diagnostic markers and therapeutic targets in cancer.