Nuclear dots are punctate structures found in the nucleus

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 of certain cells. Nuclear bodies (NBs) were first seen as prominent interchromatin structures in the nuclei of malignant or hyperstimulated animal cells. identified using anti-sp100 autoantibodies

Anti-sp100 antibodies

Anti-sp100 antibodies are found in association with primary biliary cirrhosis. The autoimmune target of anti-sp100 is the sp100 nuclear antigen which was identified by its association with primary biliary cirrhosis...

 from primary biliary cirrhosis

Primary biliary cirrhosis

Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...

 and subsequently the promyelocytic leukemia (PML) factor, but appear also to be elevated in many autoimmune and cancerous disease. Nuclear dots are metabolically stable and resistant to nuclease digestion and salt extraction.

Structure

Simple nuclear bodies (types I and II) and the shells of complex NB (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 NB. The primary components of the nuclear dots are the proteins sp100 nuclear antigen, LYSP100(a homolog of sp100),, ISG20, PML antigen, NDP55 and 53kDa protein associated with the nuclear matrix. Other proteins, such as PIC1/SUMO-1, which are associated with nuclear pore complex 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 dot proteins appears to be involved in transcriptional active regions. Expression of PML antigen and sp100

Sp100 nuclear antigen

Sp100 nuclear antigen is an interferon stimulated antigen found in the bile duct of primary biliary cirrhosis. Histologically sp100 'dots' regions of the cell nucleus. Viral infection and mitogens affect the expression of the Sp100 autoantigen...

 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 ubiquitin

Ubiquitin

Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

 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.

Pathology

These, or similar, bodies have been found increased in the presence of lymphoid cancers and SLE (lupus). They are also observed at higher frequencies in
subacute sclerosing panencephalitis in these instances antibodies to measles shows expression and localization to the bodies.

• In Promyelocytic Leukemia (PML)
  Acute promyelocytic leukemia
  Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia , a cancer of the blood and bone marrow. It is also known as acute progranulocytic leukemia; APL; AML with t, PML-RARA and variants; FAB subtype M3 and M3 variant.In APL, there is an abnormal accumulation of immature...
  
  the oncogenic PML-RARalpha chimera disrupts normal concentration of PML into nuclear bodies. Addition of As₂0₃, retenoic acid causes remission of this leukemia by triggering their reorganization. As₂0₃ destroys the chimera, allowing new SUM0-1 ubiquitinated PML to relocalize to nuclear bodies. Retinoic acid induces a caspase-3 mediated degradation of the same chimera.