). In this study, we show that BGLF4 interacts with lamin A/C and phosphorylates lamin A protein in vitro. Using a green fluorescent protein (GFP)-lamin A system, we found that Ser-22, Ser-390, and Ser-392 of lamin A are important for the BGLF4-induced disassembly of the nuclear lamina and the EBV reactivation-mediated redistribution of nuclear lamin. Virion production and protein levels of two EBV primary envelope proteins, BFRF1 and BFLF2, were reduced significantly by the expression of GFP-lamin A(5A), which has five Ser residues replaced by Ala at amino acids 22, 390, 392, 652, and 657 of lamin A. Our data indicate that BGLF4 kinase phosphorylates lamin A/C to promote the reorganization of the nuclear lamina, which then may facilitate the interaction of BFRF1 and BFLF2s and subsequent virion maturation. UL kinases of alpha-and betaherpesviruses also induce the disassembly of the nuclear lamina through similar sites on lamin A/C, suggesting a conserved mechanism for the nuclear egress of herpesviruses.Most DNA viruses replicate and assemble their genomes into nucleocapsids in the nuclei of infected cells. To facilitate efficient replication, viruses regulate the nuclear environment by affecting cellular chromatin and nuclear lamina (30,35,40). The nuclear lamina is a thin electron-dense meshwork lining the nucleoplasmic face of the inner nuclear membrane (INM) (14, 20) and provides structural support for the major components of the nuclear envelope (36, 39). The lamina also functions as a transverse scaffold for INM proteins (e.g., emerin and lamin B receptor), chromatin proteins (histone H2A/H2B dimers), and cytoskeleton-interacting proteins (nesprin1/2) (7, 52).The nuclear lamina comprises a series of type V intermediate filaments composed of lamin types A, B1, B2, and C. Types A and C are products of RNA splicing variants of the lmnA transcripts, whereas types B1 and B2 are derived from two other genes, lmnB1 and B2 (15, 22). The INM-associated lamin B layer provides the fundamental structure of the lamina and is essential for the nuclear shape, whereas the lamin A/C layer adjacent to the nucleoplasm has more specialized functions and contributes to nuclear stiffness (7, 23, 52). Similarly to other intermediate filaments, lamins contain globular head and tail domains flanked by a central rod domain (15). The rod domains of two lamin molecules can intertwine to form dimers, whereas regions flanking the head/rod and rod/tail domains potentially interact with other lamin dimers to form longer filaments (45). Physiologically, the nuclear lamina is reorganized dynamically throughout the cell cycle via a mechanism regulated by phosphorylation. Phosphorylation by mitotic Cdc2 kinase at Ser-22, Ser-390, and Ser-392 residues on lamin A/C, or by protein kinase C (PKC) during apoptosis, leads to the depolymerization of lamin (disassembly of the nuclear lamina), which may lead to their release from the INM (11,21,44).The intact meshwork of the nuclear lamina also presents a barrier to most DNA viruses. Upon infection,...
bBGLF4 of Epstein-Barr virus (EBV) encodes a serine/threonine protein kinase that phosphorylates multiple viral and cellular substrates to optimize the cellular environment for viral DNA replication and the nuclear egress of viral nucleocapsids. BGLF4 is expressed predominantly in the nucleus at early and late stages of virus replication, while a small portion of BGLF4 is distributed in the cytoplasm at the late stage of virus replication and packaged into the virion. Here, we analyzed systematically the functional domains crucial for nuclear localization of BGLF4 and found that both the N and C termini play important modulating roles. Analysis of amino acid substitution mutants revealed that the C terminus of BGLF4 does not contain a conventional nuclear localization signal (NLS). Additionally, deletion of the C-terminal putative helical regions at amino acids 386 to 393 and 410 to 419 diminished the nuclear translocation of BGLF4, indicating that the secondary structure of the C terminus is important for the localization of BGLF4. The green fluorescent protein-fused wild-type or C-terminal helical regions of BGLF4 associate with phenylalanine/glycine repeat-containing nucleoporins (Nups) in nuclear envelope fractionation. Both coimmunoprecipitation and in vitro pull-down assays further demonstrated that BGLF4 binds to Nup62 and Nup153. Remarkably, nuclear import assay with permeabilized HeLa cells demonstrated that BGLF4 translocated into nucleus independent of cytosolic factors. Data presented here suggest that BGLF4 employs a novel mechanism through direct interactions with nucleoporins for its nuclear targeting. E pstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that infects most of the human population worldwide (64).Upon stimulation of various kinds, the latent virus may be reactivated through expression of the viral immediate-early transactivators Zta and Rta, which then turn on the expression cascade of viral genes (39, 41). BGLF4 kinase is a virion-associated serine/ threonine kinase expressed during the early and late stages of the lytic cycle (55). Several viral proteins expressed at different stages of virus replication have been shown to be phosphorylated by BGLF4, including EBNA2, EBNA-LP, BMRF1, BZLF1, viral DNA replication proteins, and structural components (3,26,27,61,65,66). In cells replicating EBV, BGLF4 colocalizes with the viral DNA polymerase processivity factor BMRF1 in the viral DNA replication compartment and phosphorylates BMRF1 at multiple sites in vitro and in vivo (55,61). BGLF4 phosphorylates the cellular replication origin binding complex MCM4-MCM6-MCM7, leading to inhibition of its helicase activities (31). Our study also indicated that BGLF4 recruits the cellular nucleotide excision repair protein XPC to the viral replication compartment to enhance viral DNA replication (40). Expression of BGLF4 alone in transfected cells induces premature chromosome condensation through the activation of condensin and topoisomerase II (33). Most importantly, small interfering RNA expe...
Interfacial Dzyaloshinskii-Moriya interaction (DMI) has long been observed in normal metal/ferromagnetic multilayers, enabling the formation of chiral domain walls, skyrmions and other 2D antisymmetric spin textures confined within a single ferromagnetic layer, while more recent works on interlayer DMI reveal new pathways in realizing novel chiral 3D spin textures between two separate layers. Here, we report on interlayer DMI between two orthogonally magnetized ferromagnetic layers (CoFeB/Co) mediated by a Pt layer, and confirm the chiral nature of the observed effective field of up to 37 Oe through asymmetric hysteresis loops under in-plane field. We highlight the importance of growth-induced in-plane symmetry breaking, resulting in a sizable interlayer DMI and a universal characteristic vector through wedge deposition of the samples. We further perform deterministic current-driven magnetization switching in the perpendicularly magnetized Co layer utilizing solely the effective field from the interlayer DMI. These results demonstrate interlayer DMI's potential to facilitate deterministic field-free switching in spin memory applications.
The η 3 -allylic complex 8 was obtained from thermolysis of the neutral ruthenium furyl complex 7 with an unsaturated carbon chain on the furyl ligand. Protonation of complex 8c with HBF 4 generates complex 9c with an oxygen atom and an olefin group coordinated to the ruthenium metal.
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