In addition to the N-terminus kinase domain, there are two conserved polo-box regions of 30 amino acids at the C-terminus.

Kinase activity is regulated at least in part, by the polo-boxes that are functionally important for both auto-inhibition and subcellular localization.

S. cerevisiae polo kinase CDC5 is required to phosphorylate and remove meiotic cohesion during the first cell division.

[9] PLK1 functions during meiotic centrosome biogenesis in mouse spermatocytes, thus facilitating accurate chromosome segregation during spermatogenesis.

Abnormal centrosome amplification may lead to multipolar spindles and results in unequal segregation of chromosomes.

Retinoblastoma tumor suppressor (RB) pathway activation results in the repression of PLK1 promoter in a SWI/SNF chromatin remodeling complex dependent manner.

[13][14] PLK1 inhibitor volasertib is being evaluated in clinical trials for use in acute myeloid leukemia (AML).

[15] A combination of PLK1 and EGFR inhibition overcomes T790M-mediated drug resistance in vitro and in vivo in non-small cell lung cancer (NSCLC).

The combination of cMet and Plk1 inhibition led to significant tumor regression in NSCLC in vivo models treated with clinically relevant drugs.