FEATURES

FAMILY

DESCRIPTION

Also known as LATS1_HUMAN, LATS1, WARTS. 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). Complexes with CDK1 in early mitosis (PubMed:9988268). LATS1-associated CDK1 has no mitotic cyclin partner and no apparent kinase activity (PubMed:9988268). Binds phosphorylated ZYX, locating this protein to the mitotic spindle and suggesting a role for actin regulatory proteins during mitosis (PubMed:10831611). Binds to and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis (PubMed:15220930). Interacts (via PPxY motif 2) with YAP1 (via WW domains) (PubMed:18158288). Interacts with MOB1A and MOB1B (PubMed:19739119). Interacts with LIMD1, WTIP and AJUBA (PubMed:20303269). Interacts with ESR1, DCAF1 and DCAF13; probably recruits DCAF1 and DCAF13 to ESR1 to promote ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:28068668). Interacts with STK3/MST2; this interaction is inhibited in the presence of DLG5 (PubMed:28087714). Interacts with SCRIB in the presence of DLG5 (PubMed:28169360). Interacts with WWTR1/TAZ (By similarity).

EXTERNAL LINKS

LATS1

Mutations

Mutation(s) distribution

Mutations table