ELK-1 ubiquitination status and transcriptional activity are modulated independently of F-Box protein FBXO25.
J Biol Chem
; 296: 100214, 2021.
Article
em En
| MEDLINE
| ID: mdl-33428929
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 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
/
Transcrição Gênica
/
Processamento de Proteína Pós-Traducional
/
Proteínas F-Box
/
Proteínas Elk-1 do Domínio ets
/
Proteínas do Tecido Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article