Nuclear bodies (also known as nuclear domains, or nuclear dots) are membraneless structures found in the

cell nuclei The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

cells. Nuclear bodies include

Cajal bodies Cajal bodies (CBs) also coiled bodies, are spherical nuclear bodies of 0.3–1.0 µm in diameter found in the nucleus of proliferative cells like embryonic cells and tumor cells, or metabolically active cells like neurons. CBs are membrane ...

, the

nucleolus The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of sig ...

, and

promyelocytic leukemia protein Promyelocytic leukemia protein (PML) (also known as MYL, RNF71, PP8675 or TRIM19) is the protein product of the PML gene. PML protein is a tumor suppressor protein required for the assembly of a number of nuclear structures, called PML-nuclear bod ...

(PML) nuclear bodies (also called PML oncogenic dots). Nuclear bodies also include ND10s. ND stands for nuclear domain, and 10 refers to the number of dots seen. Nuclear bodies were first seen as prominent interchromatin structures in the nuclei of malignant or hyperstimulated animal cells identified using anti-sp100 autoantibodies from

primary biliary cirrhosis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build ...

and subsequently the promyelocytic leukemia (PML) factor, but appear also to be elevated in many autoimmune and cancerous diseases. Nuclear dots are metabolically stable and resistant to nuclease digestion and salt extraction. A nuclear body subtype is a clastosome suggested to be a site of protein degradation.

Structure

Formation and examples of nuclear membraneless compartments

Simple nuclear bodies (types I and II) and the shells of complex nuclear bodies (types III, IVa and V) consist of a non-chromatinic fibrillar material which is most likely proteinaceous. That nuclear bodies co-isolated with the nuclear matrix, and were linked to the fibrogranular nuclear matrix component by projections from the surface of the nuclear bodies. The primary components of the nuclear dots are the proteins sp100 nuclear antigen, LYSP100(a homolog of sp100), ISG20,

PML antigen PML may refer to: * Pakistan Muslim League, several Pakistani political parties * Partido Movimiento Libertario, libertarian political party in Costa Rica * Plymouth Marine Laboratory, England * Probable maximum loss, in insurance In technology * ...

, NDP55 and 53kDa protein associated with the nuclear matrix. Other proteins, such as PIC1/SUMO-1, which are associated with

nuclear pore complex A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes ...

also associate with nuclear dots. The proteins can reorganize in the nucleus, by increasing number of dispersion in response to different stress (stimulation or heat shock, respectively).

Function

One of the nuclear body proteins appears to be involved in transcriptional active regions. Expression of PML antigen and sp100 is responsive to interferons. Sp100 seems to have transcriptional transactivating properties. PML protein was reported to suppress growth and transformation, and specifically inhibits the infection of vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus, but not other types of viruses. The

SUMO-1 Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the ''SUMO1'' gene. Function This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein a ...

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

like protein is responsible for modifying PML protein such that it is targeted to dots. whereas overexpression of PML results in programmed cell death. One hypothesized function of the dots is as a 'nuclear dump' or 'storage depot'. The nuclear bodies may not all perform the same function. Sp140 associates with certain bodies and appears to be involved in transcriptional activation. ND10 nuclear bodies have been shown to play a major role in

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

regulation.

Pathology

These, or similar, bodies have been found increased in the presence of lymphoid cancers and

SLE Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...

(lupus). They are also observed at higher frequencies in

subacute sclerosing panencephalitis Subacute sclerosing panencephalitis (SSPE)—also known as Dawson disease—is a rare form of chronic, progressive brain inflammation caused by slow infection with certain defective strains of hypermutated measles virus. The condition primarily ...

; in this instance, antibodies to

measles Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...

show expression in and localization to the nuclear bodies. * In promyelocytic leukemia (PML), the oncogenic PML-

retinoic acid receptor alpha Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1) is a nuclear receptor that in humans is encoded by the ''RARA'' gene. NR1B1 is a gene with a protein product and has a chromosomal locat ...

(RARalpha) chimera disrupts the normal concentration of PML in nuclear bodies. Administration of

arsenic trioxide Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication. As an industrial chemical, whose major uses include in the manufacture of wood preservatives, pesticides, and glass. As a medication, i ...

(As₂O₃) plus

all-trans retinoic acid Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth f ...

(Tretinoin) causes remission of this leukemia by triggering the bodies' reorganization. As₂O₃ destroys the chimera, allowing new

ubiquitinated PML to relocalize to nuclear bodies. Retinoic acid induces a caspase-3 mediated degradation of the same chimera. * In HHV,

ICP0 Human Herpes Virus (HHV) Infected Cell Polypeptide 0 (ICP0) is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage ...

disrupts nuclear dots in the early stage of infection.

References

{{Nucleus Autoimmune diseases D Autoantigens Cell nucleus