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

ABSTRACT: 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 post-translational control, including phosphorylation, SUMOylation and ubiquitination. Recently, removal of mono-ubiquitin 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 co-immunoprecipitation 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 towards 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.

SUBMITTER: Quintero-Barceinas RS

PROVIDER: S-EPMC7948486 | biostudies-literature |

REPOSITORIES: biostudies-literature

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