Biological Activity

• DescriptionLATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ^[1]. TRULI is an inhibitor of both Lats 1 and Lats 2. It blocks the final kinases in Hippo signaling pathwayLats1 and Lats2, and led decrease of Yap phosphorylation. Thus elicits proliferation of several cell types that are ordinarily post-mitotic and aids regeneration in mammals^[2]. In confluent cells treated with TRULI at 10μM for 24h, protein blotting revealed that the Hippo signaling cascade was intact through the phosphorylation of the activation loops of Lats1 and Larts2. However, the phosphorylation of Yap was decreased at residue S127, which is a key site of Lats phosphorylation^[3].
• References

• [1] Furth N, Aylon Y. The LATS1 and LATS2 tumor suppressors: beyond the Hippo pathway. Cell Death Differ. 2017 Sep;24(9):1488-1501. doi: 10.1038/cdd.2017.99. Epub 2017 Jun 23. PMID: 28644436; PMCID: PMC5563998.

  [2] Kastan, N. R. et al. Development of an improved inhibitor of Lats kinases to promote regeneration of mammalian organs. BioRxiv. 2022.

  [3] Kastan, N. et al. Small-molecule inhibition of Lats kinases may promote Yap-dependent proliferation in postmitotic mammalian tissues. Nat Commun. 2021. 3100(12).