Sp100 nuclear antigen

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SP100 nuclear antigen
Identifiers
SymbolSP100
NCBI gene 6672
HGNC 11206
OMIM 604585
RefSeq NM_003113
UniProt P23497
Other data
Locus Chr. 2 q37.1
Search for
Structures Swiss-model
Domains InterPro

Sp100 nuclear antigen is an interferon stimulated antigen found in the cell nuclei of many human and higher animal cells. Autoantibodies directed against Sp100 are often found in patients with primary biliary cirrhosis. [1] Histologically Sp100 'dots' regions of the cell nucleus. Viral infection and mitogens affect the expression of the Sp100 autoantigen. Cells grown in the presence of interferons (α, β, and γ) revealed an increase both in size and number of the Sp100 protein-containing nuclear dots and increase the protein concentration. This raises "the question whether cytokine-mediated increase of Sp100 protein expression plays a role in induction of anti-Sp100 autoantibodies." [2]

Contents

Sp100 and nuclear dots

Immunofluorescence staining pattern of anti-Sp100 antibodies on HEp-20-10 cells. NUCLEAR DOTS.jpg
Immunofluorescence staining pattern of anti-Sp100 antibodies on HEp-20-10 cells.

Two proteins, Sp100 and promyelocytic leukemia (PML) factor are localized to punctate domains in the nucleus (nuclear dots or nuclear bodies). These domains (few to 20) were found to form a donut-shaped structure when cells were starved of amino acids. In particular, depravation of cystine results in most pronounced changes. [3] Two other proteins, PIC1/SUMO-1, that also interact with nuclear pore complex factors also interact with these two proteins. [4] In addition Sp100 interacts with a chromatin binding protein, HP1 alpha. [5]

Sp100 splicoforms

Some Sp100 variants contain a domain similar to two interferon-inducible nuclear phosphoproteins, suppressin and DEAF1. This defines a novel protein motif, the HNPP-box. Another class of variants has high mobility group 1 (HMG1) protein sequence as a domain. Both major classes of Sp100 splice variant proteins localize in part to nuclear dots/PML bodies and other nuclear domains. [6]

Related Research Articles

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Antinuclear antibodies are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced.

<span class="mw-page-title-main">Primary biliary cholangitis</span> Autoimmune disease of the liver

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 up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.

An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are associated with such antibodies.

<span class="mw-page-title-main">HHV Infected Cell Polypeptide 0</span> Protein

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 is known as the immediate-early or α ("alpha") phase of viral gene expression. During these early stages of infection, ICP0 protein is synthesized and transported to the nucleus of the infected host cell. Here, ICP0 promotes transcription from viral genes, disrupts structures in the nucleus known as nuclear dots or promyelocytic leukemia (PML) nuclear bodies, and alters the expression of host and viral genes in combination with a neuron specific protein. At later stages of cellular infection, ICP0 relocates to the cell cytoplasm to be incorporated into new virion particles.

<span class="mw-page-title-main">Anti-mitochondrial antibody</span> Autoantibodies against liver mitochondria, indicating primary biliary cholangitis

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<span class="mw-page-title-main">Anti-sp100 antibodies</span>

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. 20-30% of patients with primary biliary cirrhosis have sp100 Abs. The sera of these patients exhibit a characteristic "nuclear dots" pattern in indirect immunofluorescence (IIF) on Hep-2 cells.

<span class="mw-page-title-main">Nuclear bodies</span> Structures found in the cell nuclei

Nuclear bodies are membraneless structures found in the cell nuclei of eukaryotic cells. Nuclear bodies include Cajal bodies, the nucleolus, and promyelocytic leukemia protein (PML) nuclear bodies. Nuclear bodies also include ND10s. ND stands for nuclear domain, and 10 refers to the number of dots seen.

<span class="mw-page-title-main">Promyelocytic leukemia protein</span> Protein-coding gene in the species Homo sapiens

Promyelocytic leukemia protein (PML) 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 bodies, which form amongst the chromatin of the cell nucleus. These nuclear bodies are present in mammalian nuclei, at about 1 to 30 per cell nucleus. PML-NBs are known to have a number of regulatory cellular functions, including involvement in programmed cell death, genome stability, antiviral effects and controlling cell division. PML mutation or loss, and the subsequent dysregulation of these processes, has been implicated in a variety of cancers.

<span class="mw-page-title-main">Zinc finger and BTB domain-containing protein 16</span> Protein found in humans

Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.

<span class="mw-page-title-main">ILF3</span> Protein-coding gene in the species Homo sapiens

Interleukin enhancer-binding factor 3 is a protein that in humans is encoded by the ILF3 gene.

<span class="mw-page-title-main">PTPRN</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase-like N, also called "IA-2", is an enzyme that in humans is encoded by the PTPRN gene.

<span class="mw-page-title-main">ILF2</span> Protein-coding gene in the species Homo sapiens

Interleukin enhancer-binding factor 2 is a protein that in humans is encoded by the ILF2 gene.

<span class="mw-page-title-main">SOX13</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-13 is a protein that in humans is encoded by the SOX13 gene.

<span class="mw-page-title-main">SP110</span> Protein-coding gene in the species Homo sapiens

SP110 nuclear body protein is a protein that in humans is encoded by the SP110 gene.

<span class="mw-page-title-main">Anti-dsDNA antibodies</span> Group of anti-nuclear antibodies

Anti-double stranded DNA (Anti-dsDNA) antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories. They are highly diagnostic of systemic lupus erythematosus (SLE) and are implicated in the pathogenesis of lupus nephritis.

References

  1. Szostecki C, Guldner HH, Netter HJ, Will H (1990). "Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis". J. Immunol. 145 (12): 4338–47. doi: 10.4049/jimmunol.145.12.4338 . PMID   2258622. S2CID   43572051.
  2. Guldner HH, Szostecki C, Grötzinger T, Will H (1992). "IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis". J. Immunol. 149 (12): 4067–73. doi: 10.4049/jimmunol.149.12.4067 . PMID   1281200. S2CID   20921655.
  3. Kamei H (1997). "Cystine starvation induces reversible large-body formation from nuclear bodies in T24 cells". Exp. Cell Res. 237 (1): 207–16. doi:10.1006/excr.1997.3790. PMID   9417884.
  4. Sternsdorf T, Jensen K, Will H (1997). "Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1". J. Cell Biol. 139 (7): 1621–34. doi:10.1083/jcb.139.7.1621. PMC   2132645 . PMID   9412458.
  5. Seeler JS, Marchio A, Sitterlin D, Transy C, Dejean A (1998). "Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment". Proc. Natl. Acad. Sci. U.S.A. 95 (13): 7316–21. Bibcode:1998PNAS...95.7316S. doi: 10.1073/pnas.95.13.7316 . PMC   22602 . PMID   9636146.
  6. Guldner HH, Szostecki C, Schröder P, et al. (1999). "Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif". J. Cell Sci. 112. ( Pt 5) (5): 733–47. doi:10.1242/jcs.112.5.733. PMID   9973607.