LATS1

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 H1 histone 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. [provided by RefSeq]

LATS, large tumor suppressor, homolog 1 (Drosophila)

Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668).

Cell divisionIEA:UniProtKB-KW
Cellular protein localizationIEA:Ensembl
Cytoplasmic sequestering of proteinManual Assertion Based On ExperimentIMP:BHF-UCL
G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
G2/M transition of mitotic cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Hippo signalingManual Assertion Based On ExperimentIDA:BHF-UCL
Hormone-mediated signaling pathwayISS:UniProtKB
Inner cell mass cell fate commitmentIEA:Ensembl
Inner cell mass cellular morphogenesisIEA:Ensembl
TransductionManual Assertion Based On ExperimentIBA:GO_Central
Keratinocyte differentiationIEA:Ensembl
Mammary gland epithelial cell differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of cyclin-dependent protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein localization to nucleusISS:UniProtKB
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of apoptotic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of actin filament polymerizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of intracellular estrogen receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of organ growthManual Assertion Based On ExperimentIBA:GO_Central
Regulation of protein-containing complex assemblyManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of transforming growth factor beta receptor signaling pathwayISS:UniProtKB
Regulation of ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Sister chromatid segregationManual Assertion Based On ExperimentIDA:UniProtKB

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Cytoplasm, cytoskeleton, spindle
Midbody
Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body
Localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis.

Autophosphorylated and phosphorylated during M-phase of the cell cycle (PubMed:9988268, PubMed:10518011, PubMed:15122335).
Phosphorylated by STK3/MST2 at Ser-909 and Thr-1079, which results in its activation (PubMed:15688006).
Phosphorylation at Ser-464 by NUAK1 and NUAK2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy (PubMed:19927127).