Large tumor suppressor kinase 1 (LATS1) is an
enzyme that in humans is encoded by the LATS1gene.[5][6][7]
It has been associated with the
Hippo signaling pathway, where it phosphorylates YAP and
TAZ to inactivate their function.[8]
The protein encoded by this gene is a putative
serine/threonine kinase that localizes to the
mitotic apparatus and complexes with
cell cycle controller
CDC2 kinase in early
mitosis. The protein is
phosphorylated in a cell-cycle dependent manner, with late
prophase phosphorylation remaining through
metaphase. The
N-terminal region of the protein binds CDC2 to form a complex showing reduced
histone H1 kinase activity, indicating a role as a negative regulator of CDC2/
cyclin A. In addition, the
C-terminal kinase domain binds to its own N-terminal region, suggesting potential
negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a
tumor suppressor. This is supported by studies in knockout mice showing development of
soft-tissue sarcomas,
ovarian stromal cell tumors and a high sensitivity to
carcinogenic treatments.[7]
Morisaki T, Hirota T, Iida S, et al. (2002). "WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis". FEBS Lett. 529 (2–3): 319–24.
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doi:
10.1021/ac035352d.
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Yang X, Yu K, Hao Y, et al. (2004). "LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1". Nat. Cell Biol. 6 (7): 609–17.
doi:
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Chan EH, Nousiainen M, Chalamalasetty RB, et al. (2005). "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene. 24 (12): 2076–86.
doi:
10.1038/sj.onc.1208445.
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Takahashi Y, Miyoshi Y, Takahata C, et al. (2005). "Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers". Clin. Cancer Res. 11 (4): 1380–5.
doi:
10.1158/1078-0432.CCR-04-1773.
PMID15746036.
S2CID23415582.
Kuninaka S, Nomura M, Hirota T, et al. (2005). "The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death". Oncogene. 24 (34): 5287–98.
doi:
10.1038/sj.onc.1208682.
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S2CID25678521.