PLK4

Description

The PLK4 (polo like kinase 4) is a protein-coding gene located on chromosome 4.

PLK4, also known as Polo-like kinase 4, is an enzyme encoded by the PLK4 gene in humans. It belongs to the polo family of serine/threonine protein kinases and plays a crucial role in centriole duplication. PLK4 localizes to centrioles, complex microtubule-based structures found in centrosomes. Overexpression of PLK4 leads to centrosome amplification, while knockdown of PLK4 results in loss of centrosomes. PLK4 contains an N-terminal kinase domain and a C-terminal localization domain. It also possesses three polo box domains (PBDs), which facilitate oligomerization, targeting, and promote trans-autophosphorylation. PLK4 inhibitors have potential in cancer treatment, as they downregulate the expression of mitotic checkpoint kinase BubR1, leading to polyploidy and increased sensitivity to chemotherapy.

PLK4 is a serine/threonine protein kinase that plays a crucial role in centriole duplication. It initiates procentriole formation on the surface of the parental centriole, recruiting essential proteins like SASS6, CENPJ/CPAP, CCP110, CEP135, and gamma-tubulin for centriole biogenesis. Overexpression of PLK4 leads to centrosome amplification by inducing the creation of multiple procentrioles near each parental centriole during the S phase. PLK4 phosphorylates FBXW5 at Ser-151 during the G1/S transition, preventing FBXW5 from ubiquitinating SASS6. This central role in centriole replication suggests a potential link to tumorigenesis, as centrosome abnormalities are frequently observed in tumors. PLK4 is also involved in deuterosome-mediated centriole amplification in multiciliated cells, which can generate over 100 centrioles. It participates in trophoblast differentiation by phosphorylating HAND1, disrupting the interaction between HAND1 and MDFIC, and activating HAND1. PLK4 phosphorylates CDC25C and CHEK2, is required for STIL recruitment to the centriole and STIL-mediated centriole amplification (PubMed:22020124), and phosphorylates CEP131 at Ser-78 and PCM1 at Ser-372, crucial for the proper organization and integrity of centriolar satellites (PubMed:30804208).

PLK4 is also known as MCCRP2, SAK, STK18.

Associated Diseases

• Seckel syndrome
• Microcephaly and chorioretinopathy, autosomal recessive, 2
• Autosomal recessive chorioretinopathy-microcephaly syndrome