دورية أكاديمية
The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB.
| العنوان: | The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB. |
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| المؤلفون: | Albor A; Department of Dermatology and Program in Cell and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, USA. albora@ohsu.edu, El-Hizawi S, Horn EJ, Laederich M, Frosk P, Wrogemann K, Kulesz-Martin M |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2006 Sep 01; Vol. 281 (35), pp. 25850-66. Date of Electronic Publication: 2006 Jun 30. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Keratinocytes/*pathology , Muscular Dystrophies, Limb-Girdle/*genetics , NF-kappa B/*metabolism , Protein Inhibitors of Activated STAT/*chemistry , Transcription Factors/*chemistry , Ubiquitin-Protein Ligases/*chemistry, Amino Acid Sequence ; Animals ; Apoptosis ; Fibroblasts/metabolism ; Gene Expression Regulation ; Humans ; Keratinocytes/metabolism ; Mice ; Molecular Sequence Data ; Poly-ADP-Ribose Binding Proteins ; Protein Inhibitors of Activated STAT/metabolism ; Sequence Homology, Amino Acid ; Transcription Factors/metabolism ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ultraviolet Rays |
| مستخلص: | Protein inhibitors of activated STATs (PIAS) family members are ubiquitin-protein isopeptide ligase-small ubiquitin-like modifier ligases for diverse transcription factors. However, the regulation of PIAS protein activity in cells is poorly understood. Previously, we reported that expression of Trim32, a RING domain ubiquitin-protein isopeptide ligase-ubiquitin ligase mutated in human limb-girdle muscular dystrophy type 2H (LGMD2H) and Bardet-Biedl syndrome, is elevated during mouse skin carcinogenesis, protecting keratinocytes from apoptosis induced by UVB and tumor necrosis factor-alpha (TNFalpha). Here we report that Trim32 interacts with Piasy and promotes Piasy ubiquitination and degradation. Ubiquitination of Piasy by Trim32 could be reproduced in vitro using purified components. Their interaction was induced by treatment with UVB/TNFalpha and involved redistribution of Piasy from the nucleus to the cytoplasm, where it accumulated in cytoplasmic granules that colocalized with Trim32. Piasy destabilization and ubiquitination required an intact RING domain in Trim32. The LGMD2H-associated missense point mutation prevented Trim32 binding to Piasy, and human Piasy failed to colocalize with human Trim32 in fibroblasts isolated from an LGMD2H patient. Trim32 expression increased the transcriptional activity of NFkappaB in epidermal keratinocytes, both under basal treatment and after UVB/TNFalpha treatment. Conversely, Piasy inhibited NFkappaB activity under the same conditions and sensitized keratinocytes to apoptosis induced by TNFalpha and UVB. Our results indicate that, by controlling Piasy stability, Trim32 regulates UVB-induced keratinocyte apoptosis through induction of NFkappaB and suggests loss of function of Trim32 in LGMD2H. |
| معلومات مُعتمدة: | R01 CA098577 United States CA NCI NIH HHS; CA098577 United States CA NCI NIH HHS; CA69533 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (NF-kappa B) 0 (PIAS4 protein, human) 0 (Piasy protein, mouse) 0 (Poly-ADP-Ribose Binding Proteins) 0 (Protein Inhibitors of Activated STAT) 0 (Transcription Factors) 0 (Tripartite Motif Proteins) EC 2.3.2.27 (TRIM32 protein, human) EC 2.3.2.27 (TRIM32 protein, mouse) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20060704 Date Completed: 20061010 Latest Revision: 20210209 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1074/jbc.M601655200 |
| PMID: | 16816390 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0021-9258 |
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| DOI: | 10.1074/jbc.M601655200 |