serine/threonine protein kinase PLK1; polo-like kinase 1; PLK-1; serine/threonine protein kinase 13; STPK13 (PLK1 PLK)

Function

• serine/threonine protein kinase
• performs several functions throughout M phase of the cell cycle, including
  • regulation of centrosome maturation & spindle assembly
  • removal of cohesins from chromosome arms
  • inactivation of APC/C inhibitors & activation of anaphase-promoting complex/cyclosome
  • regulation of mitotic exit & cytokinesis
• required for recovery after DNA damage checkpoint & entry into mitosis
• required for kinetochore localization of BUB1B
• phosphorylates SGOL1
• required for spindle pole localization of isoform 3 of SGOL1 & plays a role in regulating its centriole cohesion function
• phosphorylates BORA, thus promotes the degradation of BORA
• contributes to the regulation of AURKA
• regulates TP53 stability through phosphorylation of TOPORS
• phosphorylates NEDD1
  • NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, a step in spindle formation
• activated by serine & threonine phosphorylation
• once activated, activity is stimulated by binding target proteins
• binding of target proteins has no effect on the non-activated kinase
• catalytic activity is enhanced by phosphorylation of Thr-210
• phosphorylation at Thr-210 is first detected on centrosomes in the G2 phase of the cell cycle, peaks in prometaphase & gradually disappears from centrosomes during anaphase
• autophosphorylation & phosphorylation of Ser-137 may not be significant for the activation of PLK1 during mitosis, but may enhance catalytic activity during recovery after DNA damage checkpoint
• ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase & following DNA damage, leading to its degradation by the proteasome
• ubiquitination is mediated via its interaction with FZR1/CDH1
• ubiquitination & subsequent degradation prevents entry into mitosis & is essential to maintain an efficient G2 DNA damage checkpoint
• interacts with CEP170 & EVI5
• interacts & phosphorylates ERCC6L
• interacts with FAM29A
• interacts with SLX4/BTBD12 & TTDN1
• interacts with BUB1B
• interacts (via POLO-box domain) with the phosphorylated form of BUB1, MLF1IP & CDC25C
• interacts with isoform 3 of SGOL1
• interacts with BORA, KIF2A & AURKA
• interacts with TOPORS & CYLD

Structure

• belongs to the protein kinase superfamily, Ser/Thr protein kinase family, CDC5/polo subfamily
• contains 2 POLO box domains
• contains 1 protein kinase domain

Compartment

• nucleus, chromosome, centromere, kinetochore
• cytoplasm, cytoskeleton, centrosome
• during early stages of mitosis, the phosphorylated form is detected on centrosomes & kinetochores
• localizes to the outer kinetochore
  • SGOL1 interaction with the phosphorylated form of BUB1 is required for the kinetochore localization

Expression

• placenta & colon
• accumulates to a maximum during the G2 & M phases
• declines to a nearly undetectable level following mitosis & throughout G1 phase
• begins to accumulate again during S phase
• induced by growth-stimulating agents

More general terms

• serine/threonine kinase
• nuclear protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5347
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5347
• OMIM: https://mirror.omim.org/entry/602098
• UniProt: http://www.uniprot.org/uniprot/P53350.html