The Hippo signaling pathway, which is involved in the regulation of cell proliferation, and an important tumor suppressor. The central regulators of the Hippo signaling pathway include the transcriptional co-activators YAP /TAZ which are negatively regulated by LATS1/2 kinases. The phosphorylation of YAP/TAZ promote their cytoplasmic sequestration where they bind with 14-3-3 protein or undergo proteasomal degradation. Dysregulation of Hippo pathway promotes the oncogenic properties of YAP/TAZ and improves cancer progression. However, the potential of YAP as a therapeutic target for cancer has not been well studied. To identify kinases-induced the phosphorylation of YAP, we screened diverse kinases which belong to CAMK family. This study demonstrated that TSSK1β promoted YAP phosphorylation partially through the LATS1/2-dependent or –independent mechanisms. Furthermore, TSSK1β consequently inhibits cell proliferation and anchorage-independent growth in LATS1/2 DKO MEFs. In summary, our findings suggest that TSSK1β can suppress YAP/TAZ-mediated cancer cell proliferation. Thus, TSSK1β can be a potential therapeutic target carcinogenesis.
