Publication Date:
2004-09-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Min -- Labuda, Tord -- Xia, Ying -- Gallagher, Ewen -- Fang, Deyu -- Liu, Yun-Cai -- Karin, Michael -- AI43477/AI/NIAID NIH HHS/ -- ES04151/ES/NIEHS NIH HHS/ -- ES06376/ES/NIEHS NIH HHS/ -- R21AI48542/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2004 Oct 8;306(5694):271-5. Epub 2004 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0723, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15358865" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD28/immunology
;
CD4-Positive T-Lymphocytes/immunology/*metabolism
;
Interferon-gamma/metabolism
;
Interleukins/metabolism
;
Lymphocyte Activation
;
*MAP Kinase Kinase Kinase 1
;
MAP Kinase Kinase Kinases/genetics/metabolism
;
Mice
;
Mitogen-Activated Protein Kinase 8
;
Mitogen-Activated Protein Kinase 9
;
Mitogen-Activated Protein Kinases/*metabolism
;
Phosphorylation
;
Proto-Oncogene Proteins c-jun/genetics/*metabolism
;
RNA, Messenger/genetics/metabolism
;
Receptors, Antigen, T-Cell/immunology
;
Recombinant Fusion Proteins/metabolism
;
T-Lymphocytes/immunology/*metabolism
;
Th2 Cells/cytology/immunology/metabolism
;
Ubiquitin/metabolism
;
Ubiquitin-Protein Ligases/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
