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FLASH GENE
Symbol PLK4 contributors: mct/npt/pgu - updated : 29-03-2018
HGNC name polo-like kinase 4
HGNC id 11397
Corresponding disease
MCCRP2 microcephaly and chorioretinopathy, autosomal recessive, 2
Location 4q28.2      Physical location : 128.802.015 - 128.820.375
Synonym name
  • polo-like kinase 4 (Drosophila)
  • SNK akin kinase
  • serine/threonine kinase 18
  • serine/threonine-protein kinase Sak
    • Synonym symbol(s) SAK, STK18, MCCRP2
    EC.number 2.7.11.21
    DNA
    TYPE functioning gene
    STRUCTURE 18.36 kb     16 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 3774 - 938 - 2008 18239451
    16 - 3830 - 970 - 2008 18239451
    16 - 3963 - 929 - 2008 18239451
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two polo box domains
    • HOMOLOGY
    interspecies ortholog to murine Stk 18
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • CDC5/Polo subfamily
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleolus
    text localizes to centrioles throughout the cell cycle and is essential for centriole duplication
  • localize exclusively at the centrosome, with none in the spindle midbody
  • PLK4 localizes to distinct subcentrosomal regions in a temporally and spatially regulated manner
    • basic FUNCTION
  • required for late mitotic progression, cell survival and postgastrulation embryonic development
  • required for centriole duplication and strongly stimulates centriole multiplication when aberrantly expressed
  • required in a dose-dependent manner for ECT2 localization to the cleavage furrow, activation of RHOA, stable positioning of the actomyosin ring, and completion of cytokinesis
  • centrioles duplicate once per cell cycle, and duplication is coordinated by PLK4
  • is a centriole-localized kinase that does not directly regulate cytokinesis
  • unexpected activity of PLK4 that promotes cell migration and may underlie an association between increased PLK4 expression, cancer progression and death from metastasis in solid tumor patients
  • ROCK2, PLK2 and PLK4 are all essential for centrosomes to re-duplicate in the cells arrested by exposure to DNA synthesis inhibitor
  • PLK4 activity promotes the recruitment of STIL to the centriole, and PLK4 primes the direct binding of STIL to the C terminus of SASS6
  • is a master regulator of centriole duplication
  • trans-autoactivation of PLK4, the trigger of centriole biogenesis, is a critical event in the spatial control of that process
  • is a critical determinant of centriolar satellite organisation
  • is required for centriolar satellite function, which may underlie the ciliogenesis defects caused by PLK4 dysfunction
    • CELLULAR PROCESS cell cycle, checkpoint
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
  • ATP
    • protein
  • interacting with CUL1 (CUL1 is critical for the degradation of active PLK4 following deregulation of cyclin E/cyclin-dependent kinase 2 activity, as is frequently observed in human cancer cells, as well as for baseline PLK4 protein stability)
  • interacting with CEP152 (recruits PLK4 and CENPJ to the centrosome to ensure a faithful centrosome duplication process)
  • FBXW52 is a substrate of both PLK4 and CDC20, two established regulators of centriole duplication
  • TUBGCP6 interacts with and is phosphorylated by PLK4
  • STIL cooperates with SASS6 and PLK4 in the control of centriole number and represents a key centriole duplication factor in human cells
  • PLK4 is a direct NFKB1 target gene
  • spatiotemporal regulation of PLK4 localization by two hierarchical scaffolds, CEP192 and CEP152, is critical for centriole biogenesis
  • removal or release of luminal SASS6 requires PLK4 and the cartwheel protein STIL
  • recruitment of ANA2 and its phosphorylation by PLK4 are the earliest known events in centriole duplication to recruit SASS6 and thereby establish the architecture of the new procentriole engaged with its parent
  • interaction between MIB1 and PLK4 is a new and important element in the control of centriole homeostasis
  • STIL protein interacts via its coiled-coil region (STIL-CC) with PLK4, mediating PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication
  • PLK4 interacts with the satellite component PCM1, and its kinase activity is required for phosphorylation of the conserved S372
  • CEP78 is a centrosomal protein and a new interaction partner of PLK4
  • KAT2A/KAT2B acetylation of PLK4 prevents centrosome amplification
  • TIAM1 regulates PLK4 levels through promoting BTRC-mediated degradation independently of RAC1 activation
    • cell & other
    REGULATION
    Phosphorylated by is directly phosphorylated and activated by stress-activated protein kinase kinase kinases MAP2K4
    Other SAKA is controled in a cell cycle-dependent manner (for cell growth and maintenance of nuclear integrity during cell division)
    centrioles promote PLK4 activation through its recruitment and local accumulation
    ASSOCIATED DISORDERS
    corresponding disease(s) MCCRP2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in hepatocellular carcinomas
    constitutional     --over  
    in cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole
    constitutional germinal mutation      
    might be a cause of Sertoli cell-only syndrome (SCOS) and nonobstructive azoospermia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice overexpressing Plk4 develop grey hair due to a loss of differentiated melanocytes and bald patches of skin associated with a thickening of the epidermis
  • Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss