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The PHD Domain of MEKK1 Acts as an E3 Ubiquitin Ligase and Mediates Ubiquitination and Degradation of ERK1/2
- Source :
- Molecular Cell. 9:945-956
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- ERK1/2 MAP kinases are important regulators in cellular signaling, whose activity is normally reversibly regulated by threonine-tyrosine phosphorylation. In contrast, we have found that stress-induced ERK1/2 activity is downregulated by ubiquitin/proteasome-mediated degradation of ERK1/2. The PHD domain of MEKK1, a RING finger-like structure, exhibited E3 ubiquitin ligase activity toward ERK2 in vitro and in vivo. Moreover, both MEKK1 kinase activity and the docking motif on ERK1/2 were involved in ERK1/2 ubiquitination. Significantly, cells expressing ERK2 with the docking motif mutation were resistant to sorbitol-induced apoptosis. Therefore, MEKK1 functions not only as an upstream activator of the ERK and JNK through its kinase domain, but also as an E3 ligase through its PHD domain, providing a negative regulatory mechanism for decreasing ERK1/2 activity.
- Subjects :
- MAPK/ERK pathway
Proteasome Endopeptidase Complex
Cell signaling
Ubiquitin-Protein Ligases
Molecular Sequence Data
Down-Regulation
MAP Kinase Kinase Kinase 1
Protein Serine-Threonine Kinases
Biology
Transfection
Ligases
Mice
Structure-Activity Relationship
Ubiquitin
Multienzyme Complexes
Tumor Cells, Cultured
Animals
Humans
Sorbitol
Amino Acid Sequence
Phosphorylation
Kinase activity
Ubiquitins
Molecular Biology
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Epidermal Growth Factor
Kinase
3T3 Cells
Cell Biology
Rats
Ubiquitin ligase
Enzyme Activation
Cysteine Endopeptidases
Blood
Biochemistry
Protein kinase domain
Mutagenesis, Site-Directed
biology.protein
Mitogen-Activated Protein Kinases
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....1d1f487deca5b1b461bbd1ccbff277e7