The latency-associated nuclear antigen or LANA-1, is a Kaposi's sarcoma

Kaposi's sarcoma

Kaposi's sarcoma is a tumor caused by Human herpesvirus 8 , also known as Kaposi's sarcoma-associated herpesvirus . It was originally described by Moritz Kaposi , a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more widely known as one of the AIDS defining...

-associated herpesvirus (KSHV

Kaposi's sarcoma-associated herpesvirus

Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...

) latent protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which has been suspected of playing a crucial role in modulating viral and cellular gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 expression.. LANA was found by Moore and colleagues as a speckled nuclear antigen present in primary effusion lymphoma cells that reacts with antibodies from patients with KS. It is commonly used as an antigen in blood tests to detect antibodies in persons that have been exposed to KSHV.

KSHV or Human herpesvirus 8 (HHV-8) has been identified as the etiological agent of Kaposi’s sarcoma (KS) and certain AIDS

AIDS

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

-associated lymphomas.
As KSHV establishes latent infection in tumorous foci, it invariably expresses high levels of the viral LANA protein, which is necessary and sufficient to maintain the KSHV episome.

Encoded by ORF73, LANA-1 is one of few HHV-8 encoded proteins that is highly expressed in all latently infected tumour cells; specifically, it is a 222–234 kDa phosphoprotein

Phosphoprotein

Phosphoproteins are proteins that are physically bonded to a substance containing phosphoric acid . This category of organic molecules includes Fc receptors, Ulks, Calcineurins, K chips, and urocortins....

 with an acidic internal repeat domain flanked by a carboxy-terminal domain and an amino-terminal domain. LANA-1 acts as a transcriptional regulator, and it has been implicated directly in oncogenesis because of its ability to bind to the tumour-suppressing protein p53

P53

p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

 and to the retinoblastoma

Retinoblastoma

Retinoblastoma is a rapidly developing cancer that develops in the cells of retina, the light-detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into...

 protein pRb

PRB

PRB may refer to:* PRB , the Australian Automotive Manufacturer* PRB * The unofficial ISO 4217 code for the Transnistrian rublePRB is short for:* Powder River Basin, a major coal producing geologic basin in the USA...

. This leads to the inactivation of p53-dependent promoters and induction of E2F-dependent genes.

Studies have also shown that LANA-1 can transactivate the promoter of the reverse transcriptase

Reverse transcriptase

In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...

 subunit of the human telomerase

Telomerase

Telomerase is an enzyme that adds DNA sequence repeats to the 3' end of DNA strands in the telomere regions, which are found at the ends of eukaryotic chromosomes. This region of repeated nucleotide called telomeres contains non-coding DNA material and prevents constant loss of important DNA from...

 holoenzyme, thus overextending a critical step in cellular transformation.
Paradoxically, LANA-1 has been shown to be involved in transcriptional repression and can, moreover, interact with the mSin3/HDAC1 co-repressor complex.

It has been also shown to interact with and inhibit the ATF4/CREB2

ATF4

Activating transcription factor 4 , also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.- Function :...

 transcription factor that interacts with the basic transcription machinery and to bind with two human chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

-associated cellular proteins, MeCP2

MECP2

MECP2 is a gene that provides instructions for making its protein product, MECP2, also referred to as MeCP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels...

 and DEK

DEK (gene)

Protein DEK is a protein that in humans is encoded by the DEK gene.-Interactions:DEK has been shown to interact with TFAP2A.-Further reading:...

.

LANA-1 is associated with cellular chromatin

Chromatin

Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

and stays on the chromosomes during cell division. It maintains the viral genomes during cell division by tethering the viral episomes to the chromosomes. It binds directly to replication origin recognition complexes (ORCs) that are primarily associated with the terminal repeat (TR) region of the HHV-8 genome.