1,721,076 research outputs found
Tripartite Motif 22 and Class II Transactivator Restriction Factors: Unveiling Their Concerted Action against Retroviruses
Full text linkCoevolution of the three basic mechanisms of immunity, intrinsic, innate and adaptive, is a constant feature of the host defense against pathogens. Within this frame, a peculiar role is played by restriction factors (RFs), elements of intrinsic immunity that interfere with viral life cycle. Often considered as molecules whose specific functions are distinct and unrelated among themselves recent results indicate instead, at least for some of them, a concerted action against the pathogen. Here we review recent findings on the antiviral activity of tripartite motif 22 (TRIM22) and class II transactivator (CIITA), first discovered as human immunodeficiency virus 1 RFs, but endowed with general antiviral activity. TRIM22 and CIITA provide the first example of cellular proteins acting together to potentiate their intrinsic immunity
HTLV-1 Infection and Adult T Cell Leukemia Mechanisms of Oncogenesis and Alteration of Immunity
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The neuron specific Ras-exchange factor Ras-GRF1 assembles with polymerized tubulin: microscopy analysis and biochemical studies
No full textMutations in specific aminoacid residues confer ph sensitivity to the rat gaba cotrasporter Gat1
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The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-kappa B by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein
Full text linkHuman T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-kappa B pathway is constitutively activated by Tax-1, which binds to NF-kappa B proteins and activates the I kappa B kinase (IKK). Upon phosphorylation-dependent I kappa B degradation, NF-kappa B migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-kappa B pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-kappa B activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKK gamma and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/I kappa B complex in the cytoplasm. Nuclear CIITA associates with Tax-1/RelA in nuclear bodies, blocking Tax-1-dependent activation of NF-kappa B-responsive genes. Thus, CIITA inhibits cytoplasmic and nuclear steps of Tax-1-mediated NF-kappa B activation. These results, together with our previous finding that CIITA acts as a restriction factor inhibiting Tax-1-promoted HTLV-1 gene expression and replication, indicate that CIITA is a versatile molecule that might also counteract Tax-1 transforming activity. Unveiling the molecular basis of CIITA-mediated inhibition of Tax-1 functions may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential
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