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rdf:type |
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lifeskim:mentions |
umls-concept:C0009221,
umls-concept:C0038435,
umls-concept:C0205145,
umls-concept:C0205164,
umls-concept:C0205360,
umls-concept:C0348080,
umls-concept:C0597298,
umls-concept:C0678226,
umls-concept:C1426212,
umls-concept:C1519751,
umls-concept:C1523987,
umls-concept:C1704686
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pubmed:issue |
4
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pubmed:dateCreated |
2003-1-20
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pubmed:abstractText |
The suppressor of cytokine signaling-3 (SOCS3/CIS-33/SSI-3) is an important negative regulator of cytokine signaling. Here, we show that an N-terminal truncated isoform (DeltaN-SOCS3) translated from the internal AUG codon 12 was profoundly induced by endoplasmic reticulum (ER) stress- or active double-stranded RNA-activated protein kinase PKR, as a result of induction of eukaryotic initiation factor 2alpha phosphorylation. DeltaN-SOCS3 exhibited a stronger cytokine-inhibitory activity and a higher stability than WT-SOCS3 in Ba/F3 hematopoietic cells. A potential ubiquitination residue, Lys-6, at the N terminus is evolutionary conserved among SOCS3 species. The K6Q-SOCS3 mutant showed a much longer half-life than WT-SOCS3 in Ba/F3 cells. Furthermore, inhibition of the 26 S proteasome pathway increased both ubiquitination and protein levels of WT-SOCS3 but had no effect on K6Q-SOCS3. SOCS3 mutant lacking the carboxyl-terminal SOCS-box exhibited the same stability as K6Q-SOCS3. These observations suggest that the short form of SOCS3 is a naturally occurring stabilized inhibitory protein, whereas WT-SOCS3 is a short-lived protein modulated by Lys-6 ubiquitination and proteasome-dependent degradation. Our findings provide strong evidence for the first time that translational control plays an important role in stabilization and function of SOCS3.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Codon,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SOCS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2432-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12459551-Animals,
pubmed-meshheading:12459551-Cell Line,
pubmed-meshheading:12459551-Codon,
pubmed-meshheading:12459551-Endoplasmic Reticulum,
pubmed-meshheading:12459551-Gene Expression Regulation,
pubmed-meshheading:12459551-Humans,
pubmed-meshheading:12459551-Lysine,
pubmed-meshheading:12459551-Mice,
pubmed-meshheading:12459551-Mutation,
pubmed-meshheading:12459551-Peptide Hydrolases,
pubmed-meshheading:12459551-Proteasome Endopeptidase Complex,
pubmed-meshheading:12459551-Protein Biosynthesis,
pubmed-meshheading:12459551-Protein Isoforms,
pubmed-meshheading:12459551-Protein Structure, Tertiary,
pubmed-meshheading:12459551-Proteins,
pubmed-meshheading:12459551-Repressor Proteins,
pubmed-meshheading:12459551-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:12459551-Time Factors,
pubmed-meshheading:12459551-Transcription Factors,
pubmed-meshheading:12459551-Transfection,
pubmed-meshheading:12459551-Ubiquitin
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pubmed:year |
2003
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pubmed:articleTitle |
The N-terminal truncated isoform of SOCS3 translated from an alternative initiation AUG codon under stress conditions is stable due to the lack of a major ubiquitination site, Lys-6.
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pubmed:affiliation |
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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