The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein actively shuttles between the nucleus, where it interacts with transcriptional and splicing regulatory proteins, and the cytoplasm, where it activates NF-B. Posttranslational modifications of Tax such as ubiquitination regulate its subcellular localization and hence its function; however, the regulation of Tax trafficking and NF-B activation by host factors is poorly understood. By screening a deubiquitinating (DUB) enzyme small interfering RNA (siRNA) library, we identified the metalloprotease STAM-binding protein-like 1 (STAMBPL1) as a positive regulator of Tax-mediated NF-B activation. Overexpression of wild-type STAMBPL1, but not a catalytically inactive mutant, enhanced Tax-mediated NF-B activation, whereas silencing of STAMBPL1 with siRNA impaired Tax activation of both the canonical and noncanonical NF-B signaling pathways. STAMBPL1 regulated Tax-induced NF-B signaling indirectly by controlling Tax nuclear/cytoplasmic transport and was required for DNA damage-induced Tax nuclear export. Together, these results reveal that the deubiquitinase STAMBPL1 is a key regulator of Tax trafficking and function.
Oncogenic transformation of CD4+ T cells by human T-cell lymphotropic virus type 1 (HTLV-1) is understood as the initial step to adult T-cell leukemia/lymphoma, a process that is mainly initiated by perturbation of cellular signaling by the viral Tax oncoprotein, a potent transcriptional regulato...
Because NF-B signaling pathways are highly conserved in evolution, the fruit fly Drosophila melanogaster provides a good model to study these cascades. We carried out an RNA interference (RNAi)-based genome-wide in vitro reporter assay screen in Drosophila for components of NF-B pathways. We anal...
Dendritic cells are sentinels in innate and adaptive immunity. Upon virus infection, a complex program is in operation, which activates IB kinase (IKK), a key regulator of inflammatory cytokines and costimulatory molecules. Here we show that the 134.5 protein, a virulence factor of herpes simplex...
There are multiple lines of evidence supporting that chronic inflammation is linked to carcinogenesis. Nuclear factor-B (NF-B), a major redox-sensitive transcription factor responsible for the induction of a wide array of pro-inflammatory genes, is frequently overactivated in many tumors. Moreove...
High-risk human papillomavirus (HR HPV) requires differentiating epithelial cells to continue to divide in order to replicate the viral DNA. To achieve this, HPV perturbs several regulatory pathways, including cellular apoptosis and senescence signals. HPV E6 has been identified as a regulator of...
The human T-lymphotropic virus type I oncoprotein Tax is critical for T-cell transformation, acting mainly through nuclear factor kappa B essential modulator (NEMO) binding and subsequent nuclear factor-B activation. Tax localizes to Tax nuclear bodies and to the centrosome and is subjected to ub...
NF-B plays a key role in innate and acquired immunity. Its activity is regulated through intricate signaling networks. Persistent or excessive activation of NF-B induces diseases, such as autoimmune disorders and malignant neoplasms. Infection by human T cell leukemia virus type 1 (HTLV-1) causes...
Nuclear factor-B (NF-B) is a master regulator of immunity and also involved in malignant transformation. It has been widely accepted that Lys-48 (K48)-linked polyubiquitination plays a critical role in NF-B signalling by targeting inhibitor of NF-B (IB), thereby leading to its degradation by the ...
submitted by wentupthehill 2 years and 5 months ago
Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) are polyA-, non-coding RNAs that are expressed abundantly in all forms of cells latently infected with EBV. EBERs (EBER1 and EBER2) contribute to the clonal proliferation of EBV-negative Burkitt's lymphoma (BL) cells in soft agar, tumorigenicity...
Although adenovirus 5 E1A-binding protein (BS69) is a nuclear protein acting as a transcriptional repressor, we found by an yeast two-hybrid and human cell immunoprecipitation another cytoplasmic function for this protein. BS69 bound Toll-interleukin 1 receptor domain (TIR)-containing adaptor mol...
