The Role of Polo-Like Kinase 1 in Regulating the Forkhead Box Family Transcription Factors

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-05, Vol.12 (9), p.1344
• Main Authors: Moore, Xavier T R, Gheghiani, Lilia, Fu, Zheng
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Angiogenesis; Apoptosis; Cancer; Care and treatment; Cell cycle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell division; Cell proliferation; Chromosomes; Cyclin-dependent kinases; DNA binding proteins; DNA damage; DNA replication; Forkhead protein; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; FOX family; FOXO1 protein; FOXO3 protein; Health aspects; Homeostasis; Humans; Kinases; Localization; Metabolism; Metastases; Mitosis; Neoplasms - genetics; oncogene; Phase transitions; Phosphorylation; Polo-like kinase; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein-serine/threonine kinase; Proteins; Review; RNA processing; RNA transport; targeted therapy; transcription factor; Transcription factors; tumor suppressor
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12091344

Polo-like kinase 1 (PLK1) is a serine/threonine kinase with more than 600 phosphorylation substrates through which it regulates many biological processes, including mitosis, apoptosis, metabolism, RNA processing, vesicle transport, and G DNA-damage checkpoint recovery, among others. Among the many PLK1 targets are members of the FOX family of transcription factors (FOX TFs), including FOXM1, FOXO1, FOXO3, and FOXK1. FOXM1 and FOXK1 have critical oncogenic roles in cancer through their antagonism of apoptotic signals and their promotion of cell proliferation, metastasis, angiogenesis, and therapeutic resistance. In contrast, FOXO1 and FOXO3 have been identified to have broad functions in maintaining cellular homeostasis. In this review, we discuss PLK1-mediated regulation of FOX TFs, highlighting the effects of PLK1 on the activity and stability of these proteins. In addition, we review the prognostic and clinical significance of these proteins in human cancers and, more importantly, the different approaches that have been used to disrupt PLK1 and FOX TF-mediated signaling networks. Furthermore, we discuss the therapeutic potential of targeting PLK1-regulated FOX TFs in human cancers.