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FLASH GENE
Symbol LATS1 contributors: mct/pgu - updated : 18-04-2016
HGNC name LATS, large tumor suppressor, homolog 1 (Drosophila)
HGNC id 6514
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region binding CDC2 to form a complex showing reduced H1 histone kinase activity and N-terminal non-kinase regions are distinct except for LATS conserved domains 1 and 2 (LCD1 and LCD2), which may be important for LATS1/2-specific functions
  • an UBA domain
  • eleven tyrosine kinase catalytic domains
  • C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding
  • HOMOLOGY
    interspecies ortholog to yeast, Dbf2
    homolog to Drosophila lats
    Homologene
    FAMILY
  • Ndr/LATS subfamily of AGC (protein kinase A/PKG/PKC) kinases
  • CATEGORY tumor suppressor , signaling , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome
    text localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis
    basic FUNCTION
  • playing a role in tumorigenesis and specific endocrine dysfunction
  • may be playing a role in the control of tumor development, by negatively regulating cell proliferation and modulating cell survival
  • controlling with LATS2 cell proliferation by negatively regulating different cell cycle check points
  • plays a crucial role in the prevention of tumor formation by controlling mitosis progression
  • may act as negative key regulators of the cell cycle
  • putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis
  • tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint
  • playing a role in mitotic exit and having abilities to induce G2 arrest and promote cytokinesis
  • role of LATS1 in controlling PLK1 at the G2 DNA damage checkpoint
  • central player of the emerging Hippo signaling pathway, which plays important roles in organ size control, tumorigenesis, and stem cell differentiation
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CDC2/LATS1 in early mitosis
  • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • Mg2+
  • protein
  • CDC2 (negative egulator of CDC2)
  • zyxin (ZYX, to control mitosis progression by forming a regulatory complex or mitotic apparatus)
  • MOBKL1A
  • MOBKL1B
  • interacts with MOB1A, a protein whose homologue in budding yeast associates with kinases involved in mitotic exit
  • can negatively regulate transcription regulation and transformation functions of YAP1 by inhibiting its nuclear translocation via phosphorylation of multiple sites in YAP1
  • interacting with the protein/discs-large protein/zonula (PDZ) domain of HTRA2 and promoting its protease activity
  • substrate for HTRA2 protease activity, thus it is not only a regulator but also a downstream target of this protease
  • LATS1 and LATS2 are novel HSP90AA1 clients and HSP90AA1 inhibitors can disrupt the LATS tumor suppressor pathway in cancer cells
  • NPHP4 inhibited LATS1-mediated phosphorylation of the Yes-associated protein (YAP1) and WWTR1, leading to derepression of these protooncogenic transcriptional regulators
  • phosphorylate Aurora B (AURKB)
  • PPP1R12A is a new substrate for LATS1 (LATS1 directly and preferentially phosphorylated serine 445 (S445) of PPP1R12A)
  • WWP1 is essential for LATS1 stability and negatively regulate LATS1 by promoting LATS1 degradation through polyubiquitination and the 26S proteasome pathway
  • disruption of the actin cytoskeleton promotes NF2-LATS1 interactions, which implicates NF2 in actin-mediated regulation of Hippo signaling
  • involved in phosphorylation of AMOT130, which is a key feature that enables it to inhibit YAP1-dependent signaling and cell growth
  • AMOT is a direct substrate of LATS1/LATS2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis
  • NEDD4 directly interacts with LATS1, leading to ubiquitination and decreased levels of LATS1 and, thus, increased YAP1 localization in the nucleus
  • LATS1, LATS2 can synergize with F-actin perturbations by phosphorylating free AMOT130 to keep it from associating with F-actin
  • AJUBa recruits LATS1 to junctions in a tension-dependent manner
  • PTPN14 and WWC1 can induce the LATS1 activation independently and cooperatively
  • LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C
  • LATS1-mediated phosphorylation of the T7 residue of CDC26 disrupts its interaction with CDC16
  • PARD3 promotes the interaction between PPP1CA and LATS1 to induce LATS1 dephosphorylation and inactivation, therefore leading to dephosphorylation and activation of TAZ
  • LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by promoter hypermethylation-mediated in astrocytoma
    tumoral     --low  
    of LATS1 and LATS2 by promoter hypermethylation is associated with a biologically aggressive phenotype in breast cancer
    tumoral germinal mutation      
    N-terminally truncated LATS1 induced LATS2 downregulation and YAP1 protein accumulation, leading to chromosomal instability and tumorigenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    may serve as a novel therapeutic target of non-small-cell lung cancer
    cancerbrain 
    useful target for astrocytoma therapy
    cancerreproductivebreast
    promising therapeutic strategy in which developed drugs targeting WWP1 cause activation of LATS1 in suppressing
    ANIMAL & CELL MODELS