Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon.

Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Research Abstract Details 

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Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Abstract Text:

Interferon (IFN)-stimulated gene (15 kDa) (ISG15) is a ubiquitin-like protein that forms covalent conjugates with cellular proteins. ISG15 is induced by IFN, microbial challenge, and p53, suggesting that it represents a genetic response that is shared among diverse stress stimuli. To investigate the regulation of this posttranslational modification pathway by a genotoxic chemotherapeutic agent, we examined ISG15 induction and conjugation in cells treated with the topoisomerase I (topoI) poison, camptothecin (CPT). CPT induced ISG15mRNA, and induction required protein synthesis and a functional p53 protein. However, IFN and the Jak-Stat components of the IFN signaling pathway were dispensable for CPT induction of ISG15. CPT induced free ISG15 and conjugates in a dose-dependent and time-dependent manner. A single 55-kDa protein was the prominent CPT-induced ISG15 conjugate and localized to the nuclear compartment. CPT-induced ISG15 conjugates were distinct from those induced by IFN; however, CPT treatment dramatically enhanced ISG15 conjugation in response to IFN. These findings provide the first evidence of a stimulus-specific induction of discrete ISG15 conjugate species and demonstrate that treatment with a combination of cancer therapeutic agents can cooperate to enhance ISG15 conjugation. Identification of the specific ISG15 conjugates induced by chemotherapeutic agents may reveal novel molecular targets.

Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Publishing Authors By Initials

For similar proteins: ubiquitins research abstracts see: proteins: ubiquitins research

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Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of interferon & cytokine research : the of

VOLUME: 24

Page Numbers: 647-54

Journal Abbreviation: J. Interferon Cytokine Res.

ISSN: 1079-9907

DAY: 6

MONTH: Nov

YEAR: 2004

Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Information

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LANGUAGE: eng

NlmUniqueID: 9507088

Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Keywords Mesh Terms:

KEYWORDS: Ubiquitins

MESH TERMS: chemistry

Chemical & Substance for Abstract: Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. Information

Substance Name: DNA Topoisomerases, Type I

Registry Number: EC 5.99.1.2

Grant and Affiliation Information for Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon.

AFFILIATION: Program in Molecular and Cell Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.

Country: United States

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MEDLINETA: J Interferon Cytokine Res

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