Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.

Speckle-type POZ protein (SPOP), a substrate-binding adaptor of the Cullin3/RING-box1 E3 ubiquitin ligase complex, induces degradative or non-degradative ubiquitination of substrates, playing a vital role in various signaling pathways, including androgen receptor (AR)/estrogen receptor (ER)-associated signal transduction, DNA damage response, and immunity. A mountain of evidence shows that cancer-associated SPOP mutations or abnormal expression of SPOP exhibit carcinogenic or tumor-suppressive properties in human diseases, such as prostate cancer or kidney cancer. In this review, we not only summarize the structure, regulation, and pathological role of SPOP, but also highlight the SPOP-interacting proteins and their structural characteristics. Based on this, we propose a novel model in which SPOP may act as a molecular bridge, facilitating interactions between its bound proteins, which provides the possibility of forming several molecular platforms, thus gathering oncoproteins closer, resulting in the appearance of certain carcinogenic characteristics of SPOP.