Abstract |
Type I interferons (IFN-alpha/-beta) are capable of suppressing c-myc mRNA expression by modulating post-transcriptional processing. However, the molecular mechanism of this phenomenon is poorly understood. We previously established that human polynucleotide phosphorylase (hPNPase(old-35)), a type I IFN-inducible 3',5' exoribonuclease involved in mRNA degradation, induces G1 cell cycle arrest and eventually apoptosis by specifically degrading c-myc mRNA. We now demonstrate a close association between IFN-beta-induced hPNPase(old-35) upregulation and c-myc downregulation in human melanoma cells. Employing stable melanoma cell clones expressing hPNPase(old-35) small inhibitory RNA, we demonstrate that hPNPase(old-35) is a key molecule coupled with IFN-beta-mediated downregulation of c-myc mRNA. Inhibition of hPNPase(old-35) or overexpression of c-myc protects melanoma cells from IFN-beta-mediated growth inhibition, emphasizing the importance of hPNPase(old-35) upregulation and consequent c-myc downregulation in IFN-beta-induced growth inhibition and apoptosis induction. In these contexts, targeted overexpression of hPNPase(old-35) might be a novel therapeutic strategy for c-myc-overexpressing and IFN-resistant tumors, such as melanomas.
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Authors | D Sarkar, E S Park, P B Fisher |
Journal | Cell death and differentiation
(Cell Death Differ)
Vol. 13
Issue 9
Pg. 1541-53
(Sep 2006)
ISSN: 1350-9047 [Print] England |
PMID | 16410805
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proto-Oncogene Proteins c-myc
- RNA, Small Interfering
- Interferon-beta
- Exoribonucleases
- PNPT1 protein, human
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Topics |
- Apoptosis
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Down-Regulation
- Exoribonucleases
(genetics, metabolism)
- Humans
- Interferon-beta
(pharmacology, physiology)
- Melanocytes
(metabolism)
- Melanoma
(metabolism)
- Proto-Oncogene Proteins c-myc
(biosynthesis, genetics)
- RNA, Small Interfering
(biosynthesis)
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