Human Large tumor suppressor homolog 1,LATS1 ELI

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).

{ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:10831611, ECO:0000269|PubMed:15122335, ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:28068668}.