PLK4

This gene encodes a member of the polo family of serine/threonine protein kinases. The protein localizes to centrioles, complex microtubule-based structures found in centrosomes, and regulates centriole duplication during the cell cycle. [provided by RefSeq]

Full Name

polo-like kinase 4 (Drosophila)

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, CENPJ/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 (PubMed:22020124).
Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208).

Biological Process

Centriole replicationManual Assertion Based On ExperimentIDA:ComplexPortal
Cilium assemblyManual Assertion Based On ExperimentIMP:UniProtKB
De novo centriole assembly involved in multi-ciliated epithelial cell differentiationISS:UniProtKB
Mitotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of centriole replicationManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cytokinesisManual Assertion Based On ExperimentIBA:GO_Central
Trophoblast giant cell differentiationISS:UniProtKB

Cellular Location

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole
Nucleus, nucleolus
Cleavage furrow
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. Associates with centrioles throughout the cell cycle. According to PubMed:16244668, it is not present at cleavage furrows.

Involvement in disease

Microcephaly and chorioretinopathy, autosomal recessive, 2 (MCCRP2):
A severe disorder characterized by microcephaly, delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities.

PTM

Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation.
Ubiquitinated; leading to its degradation by the proteasome.
Tyrosine-phosphorylated by TEC.