Mitotic Kinases Aurora-A, Plk1, and Cdk1 Interact with Elk-1 Transcription Factor through the N-Terminal Domain

• Published in: International journal of cell biology 2024, Vol.2024, p.6798897-11
• Main Authors: Uyar, Oya Arı, Babal, Yigit Koray, Yılmaz, Bayram, Kurnaz, Isil Aksan
• Format: Article
• Language: English
• Subjects: Amino acids; Antibodies; Cyclin-dependent kinases; Datasets; ETS protein; Glioma; Kinases; MAP kinase; Mitogens; Peptides; Phosphatase; Phosphoproteomes; Phosphorylation; Plasmids; Polo-like kinase 1; Protein expression; Protein kinases; Proteins; Serum response factor; Transcription factors
• ISSN: 1687-8876; 1687-8884
• DOI: 10.1155/2024/6798897

Elk-1 is a member of the ETS domain transcription factor superfamily that is phosphorylated upon mitogen-activated protein kinase (MAPK) pathway activation, which in turn regulated its interaction with partner protein serum response factor (SRF), leading to formation of a ternary complex with DNA. It has previously been reported that Elk-1 interacts with a mitotic kinase Aurora-A, although the mechanisms or the relevance of this interaction was unclear. Elk-1 was also reported to be phosphorylated by CDK5 on Thr417 residue. In this study, we show for the first time that this transcription factor interacts not only with Aurora-A but also with other mitotic kinases Aurora-B, Plk1, and Cdk1, and we define the interaction domain on Elk-1 to the first N-terminal 205 amino acids. We also describe putative phosphorylation sites of these mitotic kinases on Elk-1 and show that Elk-1 peptides containing these residues get phosphorylated by the mitotic kinases in in vitro kinase assays. We also perform bioinformatic analysis of mitotic phosphoproteomes and determine potential interaction partners for Elk-1 in Plk or Aurora phosphoproteomes. We propose that understanding the dynamic phosphorylation of Elk-1 by mitotic kinases is important and that it can present a novel target for anticancer strategies.