Serine/threonine-protein kinase PLK4

Function

Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification. Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites.

Classification

Family (Pfam)

PF00069 Pkinase, PF18190 Plk4_PB1, PF18409 Plk4_PB2

InterPro

Kinase-like_dom_sf, Plk4-like_POLO_box_2_sf, POLO_box_dom, POLO_box_Plk4_1, POLO_box_Plk4_2, POLO_box_Plk4_C, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser_Thr-PK_POLO_box_1_sf, Tyr_kinase_AS

Functional cluster

RRM RNA-Binding & Protein Kinases

Experimental structures · PDB · 17

• 2N19 NMR
• 3COK X-ray 2.25A
• 4JXF X-ray 2.40A
• 4N7V X-ray 2.76A
• 4N7Z X-ray 2.85A
• 4N9J X-ray 2.60A
• 4YUR X-ray 2.65A
• 4YYP X-ray 2.60A
• 5LHY X-ray 3.31A
• 5LHZ X-ray 2.51A
• 6N45 X-ray 2.64A
• 6N46 X-ray 3.71A
• … and 5 more

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0005814 centriole
• GO:0005813 centrosome
• GO:0032154 cleavage furrow
• GO:0005829 cytosol
• GO:0098536 deuterosome
• GO:0005730 nucleolus
• GO:0005634 nucleus
• GO:0120098 procentriole
• GO:0001741 XY body
• GO:0005524 ATP binding
• GO:0042802 identical protein binding
• GO:0106310 protein serine kinase activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0007099 centriole replication
• GO:0060271 cilium assembly
• GO:0098535 de novo centriole assembly involved in multi-ciliated epithelial cell differentiation
• GO:0046601 positive regulation of centriole replication
• GO:0006468 protein phosphorylation
• GO:0060707 trophoblast giant cell differentiation

Disease associations

• microcephaly and chorioretinopathy 2 MONDO:0014516

Drugs targeting this protein · 3

• RG-1530 inhibitor
• OCIFISERTIB inhibitor
• CFI-400945 inhibitor

Related proteins · sequence + function similarity

• Serine/threonine-protein kinase PLK4 1.00
• Serine/threonine-protein kinase PLK4 0.96
• Serine/threonine-protein kinase PLK4 0.94
• Serine/threonine-protein kinase PLK4 0.93
• Serine/threonine-protein kinase PLK4 0.90
• Serine/threonine-protein kinase PLK4 0.89
• Serine/threonine-protein kinase PLK4 0.88
• Serine/threonine-protein kinase PLK4 0.86
• Serine/threonine-protein kinase PLK4 0.86
• Serine/threonine-protein kinase PLK4 0.85
• Serine/threonine-protein kinase PLK4 0.84
• Serine/threonine-protein kinase PLK4 0.84

Co-cited proteins · studied together in the literature

• Serine/threonine-protein kinase PLK4 1 shared papers
• Spindle assembly abnormal protein 6 homolog 4 shared papers
• Centrosomal protein of 152 kDa 4 shared papers
• Serine/threonine-protein kinase PLK4 1 shared papers
• Centrosomal protein of 78 kDa 1 shared papers
• Centrosomal protein of 120 kDa 1 shared papers
• F-box/WD repeat-containing protein 5 1 shared papers
• Centrosomal P4.1-associated protein 3 shared papers
• M-phase inducer phosphatase 3 1 shared papers
• Ubiquitin carboxyl-terminal hydrolase 54 1 shared papers
• SCL-interrupting locus protein 2 shared papers
• Terminal nucleotidyltransferase 5D 1 shared papers

Literature · 28 cited papers

• Centrosomal protein 120 promotes centrosome amplification and gastric cancer progression via USP54-mediated deubiquitination of PLK4. IScience · 2023
• Structural and Functional Analyses of the FAM46C/Plk4 Complex. Structure · 2020
• Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration. J. Cell Sci. · 2020
• Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131). J. Biol. Chem. · 2019
• KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification. Nat. Commun. · 2016
• Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication. J. Cell Sci. · 2016
• Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat. Genet. · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. EMBO J. · 2011
• The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat. Cell Biol. · 2011
• Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J. Cell Biol. · 2010
• Asterless is a scaffold for the onset of centriole assembly. Nature · 2010
• … and 16 more in the literature graph