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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ahn, Young-ho Kurie, Jonathan M. |
| Description | Author Affiliation: Ahn YH ( Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.) |
| Abstract | Cells exposed to environmental stress rapidly activate the MAPK cascade (MKKK/MKK/MAPK). The transient nature of stress signaling is a consequence of negative feedback signals that lead to kinase dephosphorylation, degradation, and sequestration, which have not been fully elucidated for MKK family members. Here, we investigated the signals that negatively regulate MKK4/SEK1, an upstream activator of the MAPKs JNK and p38/HOG1. Following exposure of cells to sorbitol, MKK4 underwent ubiquitination and degradation in a proteasome-dependent manner. MKK4 ubiquitination required JNK kinase activity. The JNK substrate Itch (a HECT domain-containing Nedd4-like ubiquitin protein ligase) bound to MKK4, ubiquitinated lysines 140 and 143, and promoted MKK4 degradation. Other E3 ligases within the MAPK modular complex did not ubiquitinate MKK4. These data suggest that MKK4 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase Itch, which has a fundamental role in the mechanism that controls MKK4 protein levels. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 43 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-10-23 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | MAP Kinase Kinase 4 Metabolism MAP Kinase Signaling System Physiology Ubiquitin-Protein Ligases Ubiquitination Animals CHO Cells Cricetinae Cricetulus Genetics Drug Effects Proteasome Endopeptidase Complex Sorbitol Pharmacology Sweetening Agents Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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