LATS1

Description

The LATS1 (large tumor suppressor kinase 1) is a protein-coding gene located on chromosome 6.

Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene. It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function. 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.

== Interactions == LATS1 has been shown to interact with Zyxin and Cdk1.

LATS1 is a crucial negative regulator of YAP1 within the Hippo signaling pathway. It plays a vital role in controlling organ size and suppressing tumor development by inhibiting cell proliferation and promoting apoptosis. The core of the Hippo pathway involves a kinase cascade where STK3/MST2 and STK4/MST1, in complex with SAV1, activate LATS1/2 (in complex with MOB1). LATS1/2 then phosphorylates and inactivates YAP1 and WWTR1/TAZ. This phosphorylation blocks YAP1's nuclear translocation, preventing it from regulating genes involved in cell proliferation, death, and migration. LATS1 functions as a tumor suppressor by maintaining ploidy through its involvement in both mitotic progression and the G1 tetraploidy checkpoint. It negatively regulates the G2/M transition by downregulating CDK1 kinase activity. LATS1 is involved in p53 expression regulation and influences cytokinesis by regulating actin polymerization through LIMK1 modulation. LATS1 may also contribute to endocrine function. It plays a role in mammary gland epithelial cell differentiation, both through the Hippo pathway and the intracellular estrogen receptor signaling pathway, by promoting ESR1 degradation.

LATS1 is also known as WARTS, wts.

Associated Diseases

WES Whole Exome Sequencing