The Tumor Suppressor CYLD Interacts with TRIP and Regulates Negatively Nuclear Factor κB Activation by Tumor Necrosis Factor
| Autor: | Jia Wei Liu, Rune Toftgård, Marcel Huber, Alexandre Regamey, Priit Kogerman, Daniel Hohl, Thierry Roger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
skin tumor
Two-hybrid screening Immunology RNA-binding protein keratinocyte Animals COS Cells Hela Cells Humans NF-kappa B/*metabolism RNA-Binding Proteins/chemistry/*physiology Receptors Tumor Necrosis Factor/*physiology Signal Transduction Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Tumor Necrosis Factor-alpha/*pharmacology Tumor Suppressor Proteins/*physiology Biology Receptors Tumor Necrosis Factor Deubiquitinating Enzyme CYLD law.invention cylindroma 03 medical and health sciences 0302 clinical medicine law epidermis Immunology and Allergy Animals Humans 030304 developmental biology Genetics 0303 health sciences COS cells Tumor Necrosis Factor-alpha Tumor Suppressor Proteins Brief Definitive Report NF-kappa B RNA-Binding Proteins NFKB1 inhibition Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Cell biology 030220 oncology & carcinogenesis COS Cells Suppressor Tumor necrosis factor alpha Signal transduction HeLa Cells Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine Journal of Experimental Medicine, vol. 198, no. 12, pp. 1959-64 |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Cylindromas are benign adnexal skin tumors caused by germline mutations in the CYLD gene. In most cases the second wild-type allele is lost in tumor tissue, suggesting that CYLD functions as tumor suppressor. CYLD is a protein of 956 amino acids harboring a functional deubiquitinating domain at the COOH-terminal end. To shed more light on the function of CYLD, we have performed a yeast two hybrid screen using an HaCaT cDNA library that identified the RING finger protein TRIP (TRAF-interacting protein) as interactor with full-length CYLD. Mapping of the interacting domains revealed that the central domain of CYLD binds to the COOH-terminal end of TRIP. Far Western analysis and coimmunoprecipitations in mammalian cells confirmed that full-length CYLD binds to the COOH-terminal domain of TRIP. Because TRIP is an inhibitor of nuclear factor (NF)-kappaB activation by tumor necrosis factor (TNF), the effect of CYLD on NF-kappaB activation was investigated in HeLa cells. The results established that CYLD down-regulates NF-kappaB activation by TNF-alpha. The inhibition by CYLD depends on the presence of the central domain interacting with TRIP and its deubiquitinating activity. These findings indicate that cylindromas arise through constitutive NF-kappaB activation leading to hyperproliferation and tumor growth. |
| Databáze: | OpenAIRE |
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