SP100 nuclear antigen
Identifiers
SymbolSP100
NCBI gene6672
HGNC11206
OMIM604585
RefSeqNM_003113
UniProtP23497
Other data
LocusChr. 2 q37.1
Search for
StructuresSwiss-model
DomainsInterPro

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]

Sp100 and nuclear dots

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]

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.
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