NDLI: A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression.

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A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression.

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A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Shuhui Wright, Timothy M. Feghali, Carol A. Dingman, Jeffrey R. Hu, Bo Zhang, Yingze
Description	Author Affiliation: Hu B ( Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Biomedical Science Tower South Wing, 7th Floor, 3500 Terrace Street, Pittsburgh, PA 15261, USA.);
Abstract	There is growing evidence for the intracellular role of cytokines and growth factors, but the pathways by which these activities occur remain largely obscure. Previous work from our laboratory identified the constitutive, aberrant expression of the 31-kDa IL-1 alpha precursor (pre-IL-1 alpha) in the nuclei of fibroblasts from the lesional skin of patients with systemic sclerosis (SSc). We established that pre-IL-1 alpha expression was associated with increased fibroblast proliferation and collagen production. Further investigation has led to the identification of a mechanism by which nuclear expression of pre-IL-1 alpha affects fibroblast growth and matrix production. By using a yeast two-hybrid method, we found that pre-IL-1 alpha binds necdin, a nuclear protein with growth suppressor activity. We mapped the region of pre-IL-1 alpha responsible for necdin binding and found it to be localized near the N terminus, a region that is present on pre-IL-1 alpha, but not the mature 17-kDa cytokine. Expression studies demonstrated that pre-IL-1 alpha associates with necdin in the nuclei of mammalian cell lines and regulates cell growth and collagen expression. Our results provide the first evidence, to our knowledge, of a nuclear target for pre-IL-1 alpha. Based on these findings, we propose that the constitutively up-regulated expression of pre-IL-1 alpha in the nuclei of SSc fibroblasts up-regulates proliferation and matrix production of SSc fibroblasts through binding necdin, and by counteracting its effects on cell growth and collagen production.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Division Physiology Collagen Type I Biosynthesis Interleukin-1 Metabolism Nerve Tissue Proteins Nuclear Proteins Amino Acid Sequence Animals Binding Sites Genetics COS Cells Cell Nucleus Cells, Cultured Chemistry Molecular Sequence Data Protein Binding Protein Precursors Protein Structure, Tertiary Recombinant Proteins Transfection Two-Hybrid System Techniques Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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