Ubiquitin-Like Protein ISG15 (ISG15) is a ubiquitin-like protein that becomes conjugated to many cellular proteins upon activation by interferon-alpha and -beta. Several functions have been ascribed to the encoded protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes secreted. ISG15 becomes conjugated to a diverse set of proteins after IFN-alpha/beta stimulation or microbial challenge. The functions or biochemical consequences ISG15 conjugation to proteins are not yet known, but it appears that this modification does not target proteins for proteasomal degradation. ISG15 shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. Upon interferon treatment, ISG15 can be detected in both free and conjugated forms, and is secreted from monocytes and lymphocytes where it can function as a cytokine. In the cell, ISG15 co-localizes with intermediate filaments and ISGylation may modulate the JAK-STAT pathway or certain aspects of neurological disease.
Interferon-induced 17 kDa protein (ISG15), a 15-kDa protein of unique primary amino acid sequence, functions intracellularly as an ubiquitin homologue and a cytokine that induces production of IFN-gamma and augments NK / lymphokine-activated killer cell proliferation and function. ISG15 is secreted from monocytes and lymphocytes. ISG15 is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. Alterations in the ISG15 signalling pathway have also been found in several human tumour entities. In addition to being stimulated by type I interferon, expression of ISG15 is greatly induced by viral or bacterial infection through the Janus kinase / signal transducer and activator of transcription (Jak / STAT) signalling pathway. After induction, ISG15 is secreted by monocytes, B- and T-lymphocytes and fibroblasts. We demonstrate the novel way in which the function of the ISG15 protein is inhibited by influenza B virus, which strongly induces the ISG15 protein: a specific region of the influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of ISG15 to its target proteins both in vitro and in infected cells.
ISG15 (interferon-induced 15 kDa protein, also known as IP17) is a 15 kDa ubiquitin family protein that is expressed by a wide variety of cell types. ISG15 is induced by type-I IFN, and like ubiquitin, becomes conjugated to intracellular proteins. Unlike ubiquitin, it does not target proteins for degradation. Instead, it is part of the antivirus response. Human proISG15 is 165 amino acids (aa) in length. There are two ubiquitin-like domains (aa 2-78 and 79-157) and a propeptide (aa 158-165) that is cleaved intracellularly. Select blood mononuclear cells secrete mature ISG15, which is chemotactic for neutrophils. Mature Human ISG15 is 66% aa identical to Mouse ISG15.
Interferon-induced 17 KD protein (ISG15), a 15-KD protein of unique primary amino acid sequence, functions intracellularly as a ubiquitin homolog and a cytokine that induces production of IFN-gamma and aμgments NK / lymphokine-activated killer cell proliferation and function. ISG15 is secreted from monocytes and lymphocytes. ISG15 is a ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. Alterations in the ISG15 signaling pathway have also been found in several human tumor entities. In addition to being stimulated by type I interferon, expression of ISG15 is greatly induced by viral or bacterial infection throμgh the Janus kinase/signal transducer and activator of transcription (Jak / STAT) signaling pathway. After induction, ISG15 is secreted by monocytes, B-and T-lymphocytes, and fibroblasts. We demonstrate the novel way in which the function of the ISG15 protein is inhibited by influenza B virus, which strongly induces the ISG15 protein: a specific region of the influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of ISG15 to its target proteins both in vitro and in infected cells.
E3 ubiquitin-protein ligase Itchy homolog, also known as Atrophin-1-interacting protein 4, NFE2-associated polypeptide 1, NAPP1 and ITCH, is a cell membrane protein which contains oneC2 domain, oneHECT (E6AP-type E3 ubiquitin-protein ligase) domain and contains fourWW domains. ITCH acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation. ITCH is involved in the control of inflammatory signaling pathways. It is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. ITCH promotes the association of the complex after TNF stimulation. Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteosomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1. Defects in ITCH are the cause of syndromic multisystem autoimmune disease (SMAD) which is characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut.
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