It is well established that the human T-cell leukemia virus type 1-encoded oncoprotein Tax (Tax1) undergoes polyubiquitination as part of its mechanism to persistently activate NF-κB. However, it remains unclear whether Tax2 encoded by the closely related human T-cell leukemia virus type 2 utilizes any post-translational mechanisms to activate NF-κB. This study examines the role of ubiquitination and SUMOylation in Tax2 activation of NF-κB. The authors have demonstrated that, in contrast to Tax1, Tax2 is not conjugated by ubiquitin or SUMO proteins. Overexpression of the E2 ubiquitin-conjugating enzyme Ubc13 specifically enhances Tax1, but not Tax2, ubiquitination and NF-κB activation. Furthermore, a Tax2 lysineless mutant that is unable to be ubiquitinated, SUMOylated or acetylated retains NEMO/IKKγ interactions and activation of the NF-κB pathway. Together, these results provide evidence that Tax1 and Tax2 utilize distinct mechanisms to activate NF-κB.
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http://dx.doi.org/10.2217/fvl.13.1 | DOI Listing |
Mol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
To successfully apply the genome editing technology using the CRISPR/Cas9 system in the clinic, it is necessary to achieve a high efficiency of knock-in, which is insertion of a genetic construct into a given locus of the target cell genome. One of the approaches to increase the efficiency of knock-in is to modify donor DNA with the same Cas9 targeting sites (CTS) that are used to induce double-strand breaks (DSBs) in the cell genome (the double-cut donor method). Another approach is based on introducing truncated CTS (tCTS), including a PAM site and 16 proximal nucleotides, into the donor DNA.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Peoples' Friendship University of Russia, Moscow, 117198 Russia.
The E6 and E7 proteins of the high risk human papillomaviruses (HR HPVs) play a key role in the oncogenesis associated with papillomavirus infection. Data on the variability of these proteins are limited, and the factors affecting their variability are still poorly understood. We analyzed the variability of the currently known sequences of the HPV type 16 (HPV16) E6 and E7 proteins, taking into account their geographic origin and year of sample collection, as well as the direction of their evolution in the major geographic regions of the world.
View Article and Find Full Text PDFCommun Biol
December 2024
Institut national de la recherche scientifique (INRS)-Centre Armand-Frappier Santé Biotechnologie, 531 boulevard des Prairies, H7V 1M7, Laval, QC, Canada.
We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.
View Article and Find Full Text PDFClin Epigenetics
December 2024
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Background: Pancreatic adenocarcinoma (PDAC) exhibits a complex microenvironment with diverse cell populations influencing patient prognosis. Single-cell RNA sequencing (scRNA-seq) was used to identify prognosis-related cell types, and DNA methylation (DNAm)-based models were developed to predict outcomes based on their cellular characteristics.
Methods: We integrated scRNA-seq, bulk data, and clinical information to identify key cell populations associated with prognosis.
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