scholarly journals Evidence That the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1778
Author(s):  
Paloma Hidalgo ◽  
Arturo Pimentel ◽  
Diana Mojica-Santamaría ◽  
Konstantin von Stromberg ◽  
Helga Hofmann-Sieber ◽  
...  
Keyword(s):  
Viral Replication ◽  
Defense Mechanisms ◽  
Binding Protein ◽  
Human Adenovirus ◽  
Time Lapse ◽  
Low Complexity ◽  
Ssdna Binding ◽  
Intrinsically Disordered ◽  
Ssdna Binding Protein ◽  
Infected Cells

A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular condensates (BMCs) that assemble through liquid-liquid phase separation (LLPS). In the present work, we analyze biophysical properties of intranuclear replication compartments (RCs) induced during human adenovirus (HAdV) infection. The viral ssDNA-binding protein (DBP) is a major component of RCs that contains intrinsically disordered and low complexity proline-rich regions, features shared with proteins that drive phase transitions. Using fluorescence recovery after photobleaching (FRAP) and time-lapse studies in living HAdV-infected cells, we show that DBP-positive RCs display properties of liquid BMCs, which can fuse and divide, and eventually form an intranuclear mesh with less fluid-like features. Moreover, the transient expression of DBP recapitulates the assembly and liquid-like properties of RCs in HAdV-infected cells. These results are of relevance as they indicate that DBP may be a scaffold protein for the assembly of HAdV-RCs and should contribute to future studies on the role of BMCs in virus-host cell interactions.

scholarly journals Adenovirus 5 E1A-Mediated Suppression of p53 via FUBP1

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Jasmine Rae Frost ◽  
Megan Mendez ◽  
Andrea Michelle Soriano ◽  
Leandro Crisostomo ◽  
Oladunni Olanubi ◽  
...  
Keyword(s):  
Stress Response ◽  
Viral Replication ◽  
Rna Binding ◽  
Binding Protein ◽  
Cellular Stress ◽  
Human Adenovirus ◽  
Cellular Protein ◽  
Cellular Stress Response ◽  
Virus Growth ◽  
Adenovirus 5

ABSTRACTFar-upstream element (FUSE) binding protein 1 (FUBP1) was originally identified as a regulator of the oncogenec-Mycvia binding to the FUSE within thec-Mycpromoter and activating the expression of the gene. Recent studies have identified FUBP1 as a regulator of transcription, translation, and splicing via its DNA and RNA binding activities. Here we report the identification of FUBP1 as a novel binding partner of E1A. FUBP1 binds directly to E1A via the N terminus (residues 1 to 82) and conserved region 3 (residues 139 to 204) of adenovirus 5 E1A. The depletion of FUBP1 via short interfering RNAs (siRNA) reduces virus growth and drives the upregulation of the cellular stress response by activating the expression of p53-regulated genes. During infection, FUBP1 is relocalized within the nucleus, and it is recruited to viral promoters together with E1A while at the same time being lost from the FUSE upstream of thec-Mycpromoter. The depletion of FUBP1 affects viral and cellular gene expression. Importantly, in FUBP1-depleted cells, p53-responsive genes are upregulated, p53 occupancy on target promoters is enhanced, and histone H3 lysine 9 is hyperacetylated. This is likely due to the loss of the FUBP1-mediated suppression of p53 DNA binding. We also observed that E1A stabilizes the FUBP1-p53 complex, preventing p53 promoter binding. Together, our results identify, for the first time, FUBP1 as a novel E1A binding protein that participates in aspects of viral replication and is involved in the E1A-mediated suppression of p53 function.IMPORTANCEViral infection triggers innate cellular defense mechanisms that have evolved to block virus replication. To overcome this, viruses have counterevolved mechanisms that ensure that cellular defenses are either disarmed or not activated to guarantee successful replication. One of the key regulators of cellular stress is the tumor suppressor p53 that responds to a variety of cellular stress stimuli and safeguards the integrity of the genome. During infection, many viruses target the p53 pathway in order to deactivate it. Here we report that human adenovirus 5 coopts the cellular protein FUBP1 to prevent the activation of the p53 stress response pathway that would block viral replication. This finding adds to our understanding of p53 deactivation by adenovirus and highlights its importance in infection and innate immunity.

scholarly journals Cloning and characterisation of a nuclear, site specific ssDNA binding protein

1995 ◽  
Vol 23 (13) ◽  
pp. 2389-2395 ◽  
Author(s):  
Marten P. Smidt ◽  
Bernadetta Russchen ◽  
Lenie Snippe ◽  
Jan Wilnholds ◽  
Geert AB
Keyword(s):  
Binding Protein ◽  
Site Specific ◽  
Ssdna Binding ◽  
Nuclear Site ◽  
Ssdna Binding Protein

scholarly journals Discrimination against RNA Backbones by a ssDNA Binding Protein

Structure ◽  
2018 ◽  
Vol 26 (5) ◽  
pp. 722-733.e2 ◽  
Author(s):  
Neil R. Lloyd ◽  
Deborah S. Wuttke
Keyword(s):  
Binding Protein ◽  
Ssdna Binding ◽  
Ssdna Binding Protein

scholarly journals Overexpression, purification and helix-destabilizing properties of Epstein-Barr virus ssDNA-binding protein.

1998 ◽  
Vol 79 (5) ◽  
pp. 1257-1264 ◽  
Author(s):  
T Tsurumi ◽  
N Yokoyama ◽  
Y Yamashita ◽  
J Kishore ◽  
H Yamada ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Binding Protein ◽  
Ssdna Binding ◽  
Barr Virus ◽  
Ssdna Binding Protein ◽  
Epstein Barr

scholarly journals Identification of the mouse low-salt-eluting single-stranded DNA-binding protein as a mammalian lactate dehydrogenase-A isoenzyme

1986 ◽  
Vol 233 (3) ◽  
pp. 913-916 ◽  
Author(s):  
F S Sharief ◽  
S H Wilson ◽  
S S-L Li
Keyword(s):  
Lactate Dehydrogenase ◽  
Binding Protein ◽  
Rabbit Antiserum ◽  
Single Stranded Dna ◽  
Ssdna Binding ◽  
Low Salt ◽  
Ssdna Binding Protein ◽  
A Subunit ◽  
Cellulose Column ◽  
Mouse Myeloma

A 36,000-Mr protein purified from mouse myeloma on the basis of selective binding to a single-stranded DNA (ssDNA)-cellulose column has been identified as the lactate dehydrogenase A (LDH-A) subunit. A homogeneous preparation of this mouse myeloma ssDNA-binding protein, termed the ‘low-salt-eluting protein’, was found to possess LDH activity, and rabbit antiserum prepared against this protein was shown to cross-react with purified 36,000-Mr LDH-A subunits from mouse and bovine sources. In addition, bovine and human LHD-A4 isoenzymes were shown to be capable of binding ssDNA. These enzymic and immunological identities with LDH-A were not observed with purified helix-destabilizing protein 1 from mouse myeloma. A model for ssDNA-LDH binding is discussed.

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