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Description

Serine/threonine-protein kinase LATS1 (UniProt: O95835, also known as EC: 2.7.11.1, Large tumor suppressor homolog 1, WARTS protein kinase, h-warts) is encoded by the LATS1 (also known as WARTS) gene (Gene ID: 9113) in human. Serine/threonine-protein kinase LATS1 serves as a negative regulator of YAP1 in the Hippo signaling pathway, which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. YAP1 phosphorylation by LATS1 inhibits its translocation into the nucleus to regulate cellular genes that are important for cell proliferation, cell death, and cell migration. LATS1 is shown to be expressed in all adult tissues except in lung and kidney. LATS1 acts as a tumor suppressor and plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. It localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis. LATS1 negatively regulate G2/M transition by down-regulating CDK1 kinase activity. It is shown to be phosphorylated by STK3/MST2 at Serine 909 and Threonine 1079, which results in its activation. However, phosphorylation at Serine 464 by NUAK1 and NUAK2 leads to diminished protein level and it is essential for regulation of cellular senescence and cellular ploidy.