ELK-1 ubiquitination status and transcriptional activity are modulated independently of F-Box protein FBXO25

• Published in: The Journal of biological chemistry 2021-01, Vol.296, p.100214-100214, Article 100214
• Main Authors: Quintero-Barceinas, Reyna Sara, Gehringer, Franziska, Ducker, Charles, Saxton, Janice, Shaw, Peter E.
• Format: Article
• Language: English
• Subjects: cell proliferation; development; ETS transcription factor family; gene regulation; ubiquitin ligase; ubiquitin-specific protease 17 (USP17)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA120.014616

The mitogen-responsive, ETS-domain transcription factor ELK-1 stimulates the expression of immediate early genes at the onset of the cell cycle and participates in early developmental programming. ELK-1 is subject to multiple levels of posttranslational control, including phosphorylation, SUMOylation, and ubiquitination. Recently, removal of monoubiquitin from the ELK-1 ETS domain by the Ubiquitin Specific Protease USP17 was shown to augment ELK-1 transcriptional activity and promote cell proliferation. Here we have used coimmunoprecipitation experiments, protein turnover and ubiquitination assays, RNA-interference and gene expression analyses to examine the possibility that USP17 acts antagonistically with the F-box protein FBXO25, an E3 ubiquitin ligase previously shown to promote ELK-1 ubiquitination and degradation. Our data confirm that FBXO25 and ELK-1 interact in HEK293T cells and that FBXO25 is active toward Hand1 and HAX1, two of its other candidate substrates. However, our data indicate that FBXO25 neither promotes ubiquitination of ELK-1 nor impacts on its transcriptional activity and suggest that an E3 ubiquitin ligase other than FBXO25 regulates ELK-1 ubiquitination and function.