Abstract
The turnover of Jun proteins, like that of other transcription factors, is regulated through ubiquitin-dependent proteolysis. Usually, such processes are regulated by extracellular stimuli through phosphorylation of the target protein, which allows recognition by F box-containing E3 ubiquitin ligases. In the case of c-Jun and JunB, we found that extracellular stimuli also modulate protein turnover by regulating the activity of an E3 ligase by means of its phosphorylation. Activation of the Jun amino-terminal kinase (JNK) mitogen-activated protein kinase cascade after T cell stimulation accelerated degradation of c-Jun and JunB through phosphorylation-dependent activation of the E3 ligase Itch. This pathway modulates cytokine production by effector T cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD28 Antigens / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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Interferon-gamma / metabolism
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Interleukins / metabolism
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Lymphocyte Activation
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MAP Kinase Kinase Kinase 1*
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MAP Kinase Kinase Kinases / genetics
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MAP Kinase Kinase Kinases / metabolism
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Mice
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Antigen, T-Cell / immunology
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Recombinant Fusion Proteins / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Th2 Cells / cytology
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligases / metabolism*
Substances
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CD28 Antigens
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Interleukins
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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Ubiquitin
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Interferon-gamma
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Itch protein, mouse
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Ubiquitin-Protein Ligases
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1
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MAP Kinase Kinase Kinases
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Map3k1 protein, mouse