LATS2

Description

The LATS2 (large tumor suppressor kinase 2) is a protein-coding gene located on chromosome 13.

LATS2 (Large tumor suppressor kinase 2) is an enzyme encoded by the LATS2 gene in humans. It is a serine/threonine protein kinase belonging to the LATS tumor suppressor family and plays a crucial role in the Hippo signaling pathway. LATS2 inactivates the effector proteins YAP and WWTR1 (TAZ), which are involved in cell growth and proliferation. During interphase and mitosis, LATS2 localizes to centrosomes, interacting with proteins like aurora-A and ajuba. It is essential for the accumulation of gamma-tubulin and spindle formation during mitosis. LATS2 also interacts with a negative regulator of p53, suggesting its involvement in a positive feedback loop with p53 in response to cytoskeleton damage. Additionally, LATS2 can act as a corepressor of androgen-responsive gene expression.

LATS2 is a negative regulator of YAP1 in the Hippo signaling pathway, which plays a crucial role in controlling organ size and suppressing tumor growth by inhibiting cell proliferation and promoting apoptosis. The Hippo pathway involves a kinase cascade where STK3/MST2 and STK4/MST1, in complex with SAV1, phosphorylate and activate LATS1/2, which are in complex with MOB1. This activation leads to the phosphorylation and inactivation of YAP1 oncoprotein and WWTR1/TAZ. LATS2's phosphorylation of YAP1 prevents it from entering the nucleus, where it regulates genes involved in cell proliferation, death, and migration. LATS2 also acts as a tumor suppressor, critical for centrosome duplication, maintaining mitotic fidelity, and genomic stability. It negatively regulates the G1/S transition by downregulating cyclin E/CDK2 kinase activity. Furthermore, LATS2 is a negative regulator of the androgen receptor. Notably, it phosphorylates SNAI1 in the nucleus, causing its retention and stabilization, which promotes epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting effect is independent of its effects on YAP1 or WWTR1/TAZ.

LATS2 is also known as KPM.

Associated Diseases

WES Whole Exome Sequencing