For example, cancer-associated SPOP mutants, such as S119N, disrupt interactions with novel substrates such as cAMP response element-binding protein 5 (CREB5), impairing CREB5 ubiquitination and leading to receptor tyrosine kinase MET pathway activation, which enhances the metastatic potential of HCC cells.216. Here, CREB5 is linked to hepatocellular carcinoma.