The Epstein–Barr virus nuclear antigen 2 (EBNA-2) is one of the six EBV viral nuclear proteins expressed in latently infected

B lymphocytes B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

is a

transactivator In the context of gene regulation: transactivation is the increased rate of gene expression triggered either by biological processes or by artificial means, through the expression of an intermediate transactivator protein. In the context of recep ...

protein. EBNA2 is involved in the regulation of latent viral transcription and contributes to the immortalization of EBV infected cells. EBNA2 acts as an adapter molecule that binds to cellular sequence-specific

DNA-binding protein DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, becau ...

s, JK recombination signal-binding protein ( RBP-JK), and

PU.1 Transcription factor PU.1 is a protein that in humans is encoded by the ''SPI1'' gene. Function This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear pr ...

as well as working with multiple members of the

RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...

transcription complex.

Structure

EBNA2 has an acidic activation domain, which can interact with many different general transcription factors and co-activators. Regulation of transcription initiation and elongation by EBNA 2 is done part through

cyclin-dependent kinase 9 Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb. Function The protein encoded by this gene is a member of the cyclin-dependent kinase (CDK) family. CDK family members are highly similar to the gene produ ...

(CDK9) dependent

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

of the RNA polymerase

C-terminal domain The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

Mechanism

EBNA2 requires C-promoter binding factor 1 (CBF1) to aid in binding to its cis-responsive DNA element, the C promoter (Cp). Binding occurs during infection, to generate a 120kb transcript that encodes all nuclear antigens required for immortalization by EBV.2 Mutation of EBNA2

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

323 and 324, which are located within a highly conserved amino acid motif, abolished the interaction with CBF1.3 This same mutation also abolished the ability of EBNA-2 to activate the Cp. EBNA-LP and EBNA2 are the first two proteins expressed in latent infection of primary B lymphocytes. EBNA-LP stimulates EBNA2 activation of the LMP1 promoter and of the LMP1/LMP2B bidirectional transcriptional regulatory element whereas EBNA-LP alone only has a negative effect. EBNA2 transactivates the promoters of the latent membrane antigens LMP, TP1 and TP2. Additionally, EBNA2 interacts with an EBNA2 responsive cis-element of the TP1 promoter. Interactions with both the TP1 and LMP/TP2 promoters occur at at least one binding site for the cellular repressor protein RBP-Jκ. EBNA2 is tethered to the EBNA2 responsive promoter elements by interacting with RBP-Jκ, a human recombination signal sequence binding protein.

Specific responsive elements Specific may refer to: * Specificity (disambiguation) * Specific, a cure or therapy for a specific illness Law * Specific deterrence, focussed on an individual * Specific finding, intermediate verdict used by a jury in determining the final ...

that share the core sequence GTGGGAA have been discovered in several of the promoters activated by EBNA2. A similar core sequence has recently been identified as a binding site in RBP-Jκ. The binding of RBP-Jκ is not sufficient for EBNA2-mediated trans activation. An activated form of the Notch receptor can transactivate a reporter construct containing a

hexamer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomer, monomers.Quote: ''Oligomer molecule: A molecule of intermediate ...

of the two RBP-Jκ binding sites of the TP1 promoter. This supports the idea that EBNA2 acts as a functional equivalent of an activated

Notch receptor __NOTOC__ __FORCETOC__ Notch proteins are a Protein family, family of type 1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in Animal, animals. The Notch extracellular domain mediates i ...

. EBNA2 also interacts with the human

homolog In biology, homology is similarity in anatomical structures or genes between organisms of different taxa due to shared ancestry, ''regardless'' of current functional differences. Evolutionary biology explains homologous structures as retained her ...

of the yeast

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

(SNF5 hSNF5/Ini1) as it coelutes with both hSNF5/Ini1 and BRG1. BRG1 is a human homolog of SWI/SNF2. However, this interaction is restricted to a subpopulation of phosphorylated viral EBNA2. EBNA2-hSNF5/Ini1 interaction adds credit to the idea that EBNA2 facilitates transcriptional transactivation by acting as a transcription adapter molecule. Possibly, EBNA2 engages the hSNF-SWI complex to generate an open chromatin conformation at the EBNA2-responsive target genes. This then potentiates the function of the RBP-JK-EBNA2-polymerase II transcription complex.

References

{{DEFAULTSORT:Epstein-Barr virus nuclear antigen 2 Viral nonstructural proteins Epstein–Barr virus