| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell, Tumor, and Stem Cell Biology |
Departments of 1 Pharmacology and 2 Molecular Genetics, Microbiology, and Immunology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, New Jersey; 3 Department of Biochemistry and Molecular Biology at Louisiana State University Health Sciences Center, New Orleans, Louisiana; and 4 Department of Medicine, Cancer Institute of New Jersey, New Brunswick, New Jersey
Requests for reprints: Leroy F. Liu, Department of Pharmacology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854. Phone: 732-235-5484; Fax: 732-235-4073; E-mail: lliu{at}umdnj.edu.
IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation. (Cancer Res 2006; 66(2): 921-8)
This article has been cited by other articles:
|
|
 |
|
  C.-P. Lin, Y. Ban, Y. L. Lyu, and L. F. Liu Proteasome-dependent Processing of Topoisomerase I-DNA Adducts into DNA Double Strand Breaks at Arrested Replication Forks J. Biol. Chem., October 9, 2009; 284(41): 28084 - 28092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-M. Chi, C.-W. Lee, K.-P. Chang, S.-P. Hao, H.-M. Lee, Y. Liang, C. Hsueh, C.-J. Yu, I-N. Lee, Y.-J. Chang, et al. Enhanced Interferon Signaling Pathway in Oral Cancer Revealed by Quantitative Proteome Analysis of Microdissected Specimens Using 16O/18O Labeling and Integrated Two-dimensional LC-ESI-MALDI Tandem MS Mol. Cell. Proteomics, July 1, 2009; 8(7): 1453 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Desai, L. M. Wood, Y.-C. Tsai, T.-S. Hsieh, J. R. Marks, G. L. Scott, B. C. Giovanella, and L. F. Liu ISG15 as a novel tumor biomarker for drug sensitivity Mol. Cancer Ther., June 1, 2008; 7(6): 1430 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Shah, S. Blumen, I. Pitha-Rowe, S. Kitareewan, S. J. Freemantle, Q. Feng, and E. Dmitrovsky UBE1L represses PML/RAR{alpha} by targeting the PML domain for ISG15ylation Mol. Cancer Ther., April 1, 2008; 7(4): 905 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrmann, L. O. Lerman, and A. Lerman Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation Circ. Res., May 11, 2007; 100(9): 1276 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Okumura, W. Zou, and D.-E. Zhang ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP Genes & Dev., February 1, 2007; 21(3): 255 - 260. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
