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Proteasomes modulate conjugation to the ubiquitin-like protein, ISG15.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Liu, Mingjuan Hassel, B. A. Van |
| Copyright Year | 2003 |
| Abstract | ISG15 is a ubiquitin-like protein that is induced by interferon and microbial challenge. Ubiquitin-like proteins are covalently conjugated to cellular proteins and may intersect the ubiquitin-proteasome system via common substrates or reciprocal regulation. To investigate the relationship between ISG15 conjugation and proteasome function, we treated interferon-induced cells with proteasome inhibitors. Surprisingly, inhibition of proteasomal, but not lysosomal, proteases dramatically enhanced the level of ISG15 conjugates. The stimulation of ISG15 conjugates occurred rapidly in the absence of protein synthesis and was most dramatic in the cytoskeletal protein fraction. Inhibition of ISG15 conjugation by ATP depletion abrogated the proteasome inhibitor-dependent increase in ISG15 conjugates, suggesting that the effect was mediated by de novo conjugation, rather than protection from proteasomal degradation or inhibition of ISG15 deconjugating activity. The increase in ISG15 conjugates did not occur through a stabilization of the ISG15 E1 enzyme, UBE1L. Furthermore, simultaneous modification of proteins by both ISG15 and ubiquitin did not account for the proteasome inhibitor-dependent increase in ISG15 conjugates. These findings provide the first evidence for a link between ISG15 conjugation and proteasome function and support a model in which proteins destined for ISG15 conjugation are proteasome-regulated. |
| Starting Page | 1 |
| Ending Page | 6 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/early/2002/11/07/jbc.M208123200.full.pdf |
| PubMed reference number | 12426315v1 |
| Volume Number | 278 |
| Issue Number | 3 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Cytoskeleton ISG15 gene Immunostimulating conjugate (antigen) Proteasome inhibitor Protein Biosynthesis conjugation multicatalytic endopeptidase complex |
| Content Type | Text |
| Resource Type | Article |
