PLK1

What is PLK1 protein?

PLK1 gene (polo like kinase 1) is a protein coding gene which situated on the short arm of chromosome 16 at locus 16p12. PLK1 is a protein kinase widely studied in the field of cell cycle regulation and cancer. It plays a key role in mitosis, controlling centrosome maturation and separation, spindle assembly, chromosome arrangement and separation, and cytoplasmic division. The activity of PLK1 is essential to ensure genomic stability, and its abnormal expression or dysfunction has been associated with the occurrence and development of a variety of tumors. The function of PLK1 is not limited to mitosis, it is also involved in the regulation of DNA damage response, cell death pathway, and immune response. The PLK1 protein is consisted of 603 amino acids and PLK1 molecular weight is approximately 68.3 kDa.

What is the function of PLK1 protein?

PLK1 is involved in the maturation of centrosomes, which are essential for organizing microtubules and proper spindle formation. It contributes to the assembly of the mitotic spindle, ensuring correct attachment of microtubules to kinetochores on chromosomes. It plays a role in the final stage of cell division, cytokinesis, where the cell physically divides into two daughter cells. PLK1 is involved in the regulation of autophagy (self-eating process for cellular components recycling) and apoptosis (programmed cell death). It is implicated in the cellular response to DNA damage, participating in repair mechanisms and cell cycle arrest to prevent replication and segregation of damaged DNA.

Fig1. Role of PLK1 in mitosis. (Styliani Iliaki, 2021)

PLK1 related signaling pathway

PLK1 is a key serine/threonine kinase in cell cycle regulation and cancer research. It is mainly expressed in G2/S and M phases and controls cell entry into mitosis, centrosome maturation, spindle assembly, sister chromatid aggregation, and cytoplasmic division by phosphorylation of specific substrates. In addition to its role in mitosis, PLK1 also plays a role in areas such as DNA damage response, autophagy, apoptosis, and cytokine signaling. In cancer, PLK1 promotes cell proliferation, transformation, and epithelial-mesenchymal transformation by controlling a variety of key transcription factors.

PLK1 related diseases

The abnormal expression or dysfunction of PLK1 is associated with a variety of diseases, especially the occurrence and development of cancer. Overexpression of PLK1 is associated with poor prognosis in a variety of cancers, including but not limited to colorectal cancer, non-small cell lung cancer, breast cancer, ovarian cancer, prostate cancer, and head and neck squamous cell carcinoma. PLK1 is also implicated in immune and neurological disorders, including graft-versus-host disease, Huntington's disease, and Alzheimer's disease.

Bioapplications of PLK1

In practice, PLK1 inhibitors have made some progress as an anticancer strategy, especially in the treatment of non-small cell lung cancer (NSCLC), where PLK1 inhibitors can induce immunogenic cell death and enhance the immune response to tumors. In addition, another important application of PLK1 in cancer treatment is in combination with chemoradiotherapy or other targeted therapeutic agents. Since the single use of PLK1-targeted drugs has not achieved satisfactory efficacy in most clinical trials, the combination therapy strategy has become a new research direction and hot spot.

Case Study 1: Maeva Dufies, 2021

The expression of Polo-like kinase 1 (Plk1) is linked to worse survival in various cancers, but the mechanisms controlling its expression are not well understood. This study reveals that Plk1 contributes to metastasis and drug resistance in clear cell renal cell carcinoma (ccRCC) through a hypoxia-regulated process. Results showed that Plk1 expression is driven by HIF-2, which binds to the hypoxia response element in the Plk1 promoter. In ccRCC patients, elevated Plk1 levels were associated with shorter disease-free and overall survival. Reducing Plk1 levels significantly slowed tumor growth and metastasis. Moreover, high Plk1 expression was linked to resistance to therapies like sunitinib in ccRCC, both in preclinical models and in patients. Notably, a subset of ccRCC patients with high Plk1 expression did not respond to existing treatments.

Fig1. Plk1 and HIF-2α expression in VHL-i RCC cell lines was evaluated by immunoblotting.

Fig2. Cell death was evaluated by flow cytometry after treated with 2.5 or 5 μM sunitinib.

Case Study 2: Sol-Bi Shin, 2020

Initial research showed high PLK1 levels in cancer, prompting studies into its role in metastasis. The direct impact of PLK1 on metastasis in non-small cell lung cancer (NSCLC) and the mechanisms involved were previously unknown. Researchers have demonstrated that active PLK1, phosphorylated at T210 and induced by TGF-β in lung cells, strongly promotes metastasis in a tail-vein injection model. This active form of PLK1, with full polo-box and ATP-binding functionalities, enhances cell mobility and invasiveness by initiating epithelial-mesenchymal transition (EMT). However, a phosphomimetic version at p-S137 did not have the same effect, suggesting that specific PLK1 phosphorylation is crucial. Active PLK1 also increases TGF-β signaling and the expression of TSG6, encoded by TNFAIP6. Disruption of TNFAIP6 reduced the metastatic effects of active PLK1 or TGF-β. Clinical data indicates that PLK1 and TNFAIP6 predict poor survival in metastatic NSCLC patients.

Fig3. T210 of PLK1 is highly phosphorylated, but S137 is not in TGF-β-induced epithelial mesenchymal transition (EMT).

Fig4. Loss of PLK1 activity blocks pro-tumorigenic and pro-metastatic activity induced by active PLK1 or TGF-β.

PLK1 has several biochemical functions, for example, ATP binding,anaphase-promoting complex binding,kinase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by PLK1 itself. We selected most functions PLK1 had, and list some proteins which have the same functions with PLK1. You can find most of the proteins on our site.

PLK1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PLK1 here. Most of them are supplied by our site. Hope this information will be useful for your research of PLK1.

TP53;SLX4;FADD