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The SWIM domain of MEKK1 is required for complex formation with Jun that controls Fra‐2 ubiquitination
Author(s) -
Cuevas Bruce Daniel,
Duellman Tyler
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.963.6
Subject(s) - ubiquitin ligase , ubiquitin , c jun , microbiology and biotechnology , chemistry , map kinase kinase kinase , kinase , protein kinase a , biology , transcription factor , biochemistry , gene
The MAPK kinase kinase (MKKK) MEKK1 is unique among kinases in that it contains E3 ubiquitin ligase activity. MEKK1 has been reported to mediate ubiquitination of c‐Jun, thus requiring MEKK1/Jun complex formation, but the nature of that complex has not been described. The objective of this study was to determine if Jun forms a complex with MEKK1, and if so, characterize that interaction. Here we report that MEKK1 directly associates with the DNA‐binding region (DBD) of Jun, and this complex requires the MEKK1 SWIM domain, the function of which was previously unknown. We also demonstrate that direct interaction between the SWIM domain and AP‐1 proteins is limited to Jun proteins, and this requires amino acids conserved in the DBD of Jun, but not Fos proteins. Finally, we demonstrate that the Fos family protein Fra‐2 associates with the MEKK1 complex via Jun, and that Jun is required for MEKK1‐dependent Fra‐2 ubiquitination. Altogether, our data show that, in addition to regulating AP‐1 phosphorylation through control of MAPK activity, MEKK1, Jun, and Fra‐2 form a multi‐protein complex that regulates Fra‐2 ubiquitination. This work was supported by a grant from the National Institutes of Health.