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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Line, Cell Proliferation, Endopeptidases, F-Box Proteins, Fibroblasts, HEK293 Cells, HeLa Cells, Humans, Mice, Nerve Tissue Proteins, Phosphorylation, Plasmids, Protein Binding, Protein Processing, Post-Translational, Sequence Alignment, Sequence Homology, Amino Acid, Sumoylation, Transcription, Genetic, Transfection, Ubiquitination, ets-Domain Protein Elk-1
J Biol Chem
Date: Jan. 12, 2021
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