Regulation and function of the TAZ transcription co‐activator

The Hippo pathway regulates organ size by controlling both cell proliferation and apoptosis. We have demonstrated TAZ functions as a transcriptional co‐activator downstream of the Hippo pathway, and TEADs mediate TAZ function in promoting cell proliferation and epithelial‐mesenchymal transition(EMT)(Lei, et al, 2008, Zhang, et al, 2009). TAZ has been implicated in human cancer development. We further characterized the key step in the Hippo –TAZ pathway is phosphorylation of TAZ by LATS kinase, which leads to TAZ inhibition by both cytoplasmic retention and degradation, eventually resulting in inhibiting TAZ function (Lei et al, 2008, Liu, et al, 2010). Recently, we identified PP1 as a bona fide TAZ phosphatase. PP1A dephosphorylates TAZ at Ser89 and Ser311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase. As a result, PP1 increase TAZ dependent gene expression (Liu, et al, JBC principle accepted). Our studies demonstrate that Lats kinase and PP1A play a critical role in TAZ function by reversible dynamic phosphorylation regulation. This work was supported by the 985 Program and New Century Talent from the Chinese Ministry of Education (Grant No. NCET‐09‐0315) from the Chinese Ministry of Education, 863(Grant No. 2006AA02A308), 973 (Grant No. 2009CB918401), NSFC (Grant No. 30600112, 30871255, 31071192), Shanghai key project (Grant No. 09JC1402300) (Q. L.)