The F-box protein FBXO25 promotes the proteasome-dependent degradation of ELK-1 protein.
FBXO25 is one of the 69 known human F-box proteins that serve as specificity factors for a family of ubiquitin ligases composed of SKP1, Rbx1, Cullin1, and F-box protein (SCF1) that are involved in targeting proteins for degradation across the ubiquitin proteasome system. However, the substrates of most SCF E3 ligases remain unknown. Here, we applied an in chip ubiquitination screen using a human protein microarray to uncover putative substrates for the FBXO25 protein. Among several novel putative targets identified, the c-fos protooncogene regulator ELK-1 was characterized as the first endogenous substrate for SCF1(FBXO25) E3 ligase. FBXO25 interacted with and mediated the ubiquitination and proteasomal degradation of ELK-1 in HEK293T cells. In addition, FBXO25 overexpression suppressed induction of two ELK-1 target genes, c-fos and egr-1, in response to phorbol 12-myristate 13-acetate. Together, our findings show that FBXO25 mediates ELK-1 degradation through the ubiquitin proteasome system and thereby plays a role in regulating the activation of ELK-1 pathway in response to mitogens.
From the Departments of Biochemistry and Immunology and.
Felipe R
FR
Teixeira
Adriana O
AO
Manfiolli
Cláudia S
CS
Soares
Munira M A
MM
Baqui
Tie
T
Koide
Marcelo D
MD
Gomes
D051766:Early Growth Response Protein 1 / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D040081:Protein Array Analysis; D059748:Proteolysis; D040901:Proteomics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D025801:Ubiquitin / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism*
C497325:EGR1 protein, human; C494112:ELK1 protein, human; D051766:Early Growth Response Protein 1; D044783:F-Box Proteins; C510759:FBXO25 protein, human; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D025801:Ubiquitin; D050807:ets-Domain Protein Elk-1; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate
E3 Ubiquitin Ligase; Ets Family Transcription Factor; Proteasome; Protein Degradation; egr-1