Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 'proliferating cell nuclear antigen' (PCNA), also known as cyclin, accumulates in the nuclei of dividing and transformed cells and reacts with autoantibodies from certain lupus patients. A full-length cDNA (1195 bp) clone encoding PCNA/cyclin was isolated from rat thymocyte cDNA library. The nucleotide sequence reveals an open reading frame of 783 nucleotides coding for 28.7 kD protein. The predicted amino acid sequence and composition are in excellent agreement with the published protein data of rabbit PCNA. We report the entire nucleotide sequence of the cDNA and complete amino acid sequence for rat PCNA/cyclin.
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PMID:Molecular cloning and nucleotide sequence analysis of rat PCNA/cyclin cDNA. 288 89

In a clinical and serological follow-up study on a large series of subjects with different connective tissue disorders, anti-PCNA/cyclin autoantibodies were found in about 3% of patients with SLE. Positive subjects showed a higher incidence of diffuse proliferative glomerulonephritis and hematological disorders than the general SLE population. A highly significant serological association between PCNA and SL/Ki autoantibodies (p less than 0.001) has been observed. Persistence or disappearance of serum PCNA antibodies were independent of any clinical and serological feature or the therapeutic regimen employed.
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PMID:Autoantibody to proliferating cell nuclear antigen (PCNA) in SLE: a clinical and serological study. 289 2

Studies of growth regulation and cellular transformation will be assisted by the identification of proteins that are preferentially synthesized in dividing cells. The 'proliferating cell nuclear antigen' ( PCNA ), distinguished by its apparent association with cell division, is defined by reaction with an antibody found in the autoimmune disease systemic lupus erythematosus (SLE). This antibody reacts with proliferating cells including tumour cells but gives weak or undetectable immunofluorescence with resting cells of normal tissues. Peripheral blood lymphocytes are devoid of PCNA until activated by mitogen in vitro. In synchronized cultures its level and distribution fluctuate through the cell cycle, with a striking accumulation in the nucleolus late in the G1 phase and early in the S phase. Many of these properties are shared by ' cyclin '. This nuclear protein, identified by its position in a two-dimensional separation of cell proteins, is also transformation-sensitive and is preferentially synthesized in the S phase. We establish here that PCNA and cyclin are identical, and show that PCNA is an acidic nuclear protein of apparent molecular weight 35,000.
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PMID:Identity of the proliferating cell nuclear antigen and cyclin. 614 97

We report the course of a pregnancy of a 21-year-old primipara and primigravida with systemic lupus erythematosus (SLE) and anti-U1RNP, anti-PCNA/cyclin, anti-dsDNA and anti-phospholipid autoantibodies. The pregnancy was normal and a healthy child was born at term. The risks associated with the HLA phenotype of the mother and with these autoantibodies were previously unknown. We present a model for risk assessment in patients with rare laboratory features of SLE.
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PMID:Uncomplicated pregnancy and birth of a healthy child by a woman with systemic lupus erythematosus and anti-U1RNP, anti-PCNA/cyclin, anti-dsDNA and anti-phospholipid autoantibodies. 795 97

A general characteristic of lupus-prone mice (and humans) is the expedited accumulation of large numbers of presumably self-reactive activated/memory phenotype T cells. The mechanism by which these cells escape apoptosis has not been defined. We used activated/memory phenotype CD4+ cells from male BXSB mice with early-life severe lupus-like disease to investigate cell cycle status and apoptosis susceptibility, and to determine the role of corresponding genes in survival of these cells. In vitro acridine orange staining indicated that most of the rapidly accumulating memory phenotype CD4+ T cells of 4-month-old male BXSB mice are G1 arrested. Long-term bromodeoxyuridine in vivo labeling also showed that with advanced age, there was a shift of the CD4+ CD44(hi) male cells from predominantly cycling to predominantly noncycling. Moreover, the CD4+ CD44(hi) cells of older males were refractory to anti-CD3-induced proliferation and apoptosis. Using a multiprobe RNase protection assay encompassing riboprobe panels for cell cycle and apoptosis-related genes, we found that these cells exhibited high expression of certain members of the Ink4 (p18Ink4C) and Cip/Kip (p21Cip1) families of cyclin kinase inhibitors as well as of the apoptosis-inhibiting Bcl-xL gene. Western blot analysis confirmed increased levels of Bcl-xL and p21Cip1, and also identified increases in another cyclin kinase inhibitor, p27Kip1. We propose that in autoimmunity, self-reactive CD4+ cells are subjected to successive rounds of activation/division that eventually lead to a build-up in cyclin-dependent kinase inhibitors. Once high levels of such inhibitors are reached, they cause refractoriness to further activation, impaired cell cycle entry and resistance to apoptosis, a situation akin to replicative senescence.
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PMID:G1 arrest and high expression of cyclin kinase and apoptosis inhibitors in accumulated activated/memory phenotype CD4+ cells of older lupus mice. 929 25

Proliferating cell nuclear Ag (PCNA) occurs as a component of multiprotein complexes during cell proliferation. We found the complexes to react with murine anti-PCNA mAbs, but not with anti-PCNA Abs in lupus sera. The complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA mAbs (TOB7, TO17, and TO30) and analyzed by ELISA, immunoprecipitation, immunoblotting, and HPLC gel filtration. That PCNA was complexed with other proteins was demonstrated by its copurification with a group of proteins excluded by an HPLC G3000 SW column. Although immunoblot analysis showed the mAbs to react exclusively with the 34-kDa PCNA polypeptide, they nonetheless immunoprecipitated the same group of proteins, confirming the interaction of the isolated PCNA with other proteins. Anti-PCNA sera, including AK, which reacts with biologically functional sites on PCNA, did not react with complexed PCNA, but did react with it once it was dissociated from the complexes. PCNA complexes in turn reacted with murine anti-DNA mAbs, as well as with Abs against p21, replication protein A, DNA helicase II, cyclin-dependent kinases 4 and 5, and topoisomerase I. These findings suggest that the PCNA complexes purified using anti-PCNA mAbs comprise the "protein machinery" for DNA replication and cell cycle regulation. They also suggest that anti-PCNA mAbs are useful tools with which to characterize the protein-protein interactions within PCNA complexes, as well as the autoimmune responses to proteins interacting with PCNA, which may shed light on the mechanisms of autoantibody production in lupus patients.
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PMID:Reactivity of anti-proliferating cell nuclear antigen (PCNA) murine monoclonal antibodies and human autoantibodies to the PCNA multiprotein complexes involved in cell proliferation. 1125 41

The cyclin kinase inhibitor protein p21 affects multiple processes relevant to the immune system, including cell cycle progression, replicative senescence, hemopoietic stem cell quiescence, and apoptosis. Therefore, malfunction of this protein may be a contributor to the pathogenesis of systemic autoimmunity. Here, we report that mixed background p21-deficient 129/Sv x C57BL/6 mice showed increased in vitro and in vivo T cell cycling and activation, moderate hypergammaglobulinemia and, at low penetrance, anti-chromatin autoantibodies. Homeostatic anti-self MHC/peptide ligand-induced proliferation of p21-deficient T cells was also enhanced. However, lymphoid organ enlargement was very mild, presumably due to increased apoptosis of the rapidly dividing cells. Moreover, the older p21-deficient mice had kidney pathology representing a similar, but slightly more advanced, state than that seen in the control mice. The timing and severity of the above serologic, cellular, and histologic manifestations in p21-deficient mice were unaffected by gender. Thus, p21 deficiency significantly enhances T cell activation and homeostatic proliferation, and can induce mild autoimmune manifestations at a low incidence without gender bias, but does not in itself generate the full spectrum of lupus-like disease.
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PMID:Role of cyclin kinase inhibitor p21 in systemic autoimmunity. 1156 28


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