Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have been investigating the generation of specific immune responses using monoclonal anti-idiotypic Abs (Ab2) as surrogate tumor Ag. We have prepared a series of idiotypic mAbs (Ab1) from CBH/cbi rats bearing the syngeneic sarcoma HSN and have used these Ab1 to generate autologous Ab2. By using the autologous Ab2 as Ag, we have isolated T cell lines from CBH/cbi rats that proliferate specifically in the presence of the Ab2, with spleen cells as APC. Specific proliferation of the T cells was prevented if the spleen cells used for presentation were irradiated with conventional doses of x-rays (1000 rad) just before use. Titration of the radiation response showed that the capacity of the spleen cells to present Ag decreased exponentially with x-ray doses of up to 100 rad, at which dose presentation was virtually abolished. The same irradiated spleen cells were fully competent to present OVA to CBH/cbi-derived rat T cell lines specific for this Ag. Preincubating the APC with Ag before irradiation abrogated the effect of x-irradiation on the presentation of Ab2. We conclude that, in this rat system, the presentation of autologous Ab2 is highly sensitive to the effects of low doses of x-rays. The clinical significance of these findings is discussed.
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PMID:Presentation of anti-idiotypic antibody is sensitive to ionizing radiation. 802 96

beta-catenin interacts with a number of proteins in different important biological processes, including cell adhesion through cadherins, actin organization through fascin, body axis determination through Wnt signaling, tumor suppression through APC, and transcriptional activation through LEF-1. To examine its function in chicken embryogenesis, we isolated the chicken homolog of beta-catenin from a chicken embryo cDNA library. The sequence is highly conserved at the amino acid level between chicken, mouse (99%), human (99%) and Xenopus (97%). In-situ hybridization and immunostaining showed that in the developing limb, it is specifically expressed in the apical ectodermal ridge, suggesting a role in epithelial-mesenchymal interactions.
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PMID:Isolation and characterization of chicken beta-catenin. 932 59

Maturation of dendritic cells (DC) is critical to their development into potent APCs. Upon maturation, DC up-regulate the expression of MHC class II as well as costimulatory and adhesion molecules, all of which are important in Ag presentation. In addition, they undergo structural changes characterized by the expression of numerous long dendrites. Fascin is an actin-bundling protein that has been reported to be important for the development of dendrites. In this study, we evaluated fascin expression and function during DC maturation into potent APC. In vitro, treatment of bone marrow-derived DC (BM-DC) with GM-CSF resulted in increased levels of fascin expression. This increase correlated directly with an increase in MHC class II and B7-2 expression. Fascin expression was decreased by the addition of TGF-ss and increased by the addition TNF-alpha to the culture. These cytokines suppress or enhance DC maturation, respectively. Increased levels of fascin expression were found to correlate with increased APC activity in a one-way MLR. Specific inhibition of fascin expression, using antisense oligonucleotides, markedly reduced this APC allostimulatory activity. These data demonstrate that fascin expression correlates with DC maturation into APC, and it plays a significant role in the ability of DC to function as APC. This observation is the first evidence linking fascin-mediated dendrite formation with the APC activity of DC.
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PMID:Fascin is involved in the antigen presentation activity of mature dendritic cells. 1112 10

Rearrangements in the actin cytoskeleton play a pivotal role for costimulation-induced formation of the immunological synapse and T cell activation. Yet, little is known about the actin-binding proteins that link costimulation to rearrangements in the actin cytoskeleton. Here we demonstrate that phosphorylation of the actin bundling protein L-plastin in response to costimulation through TCR/CD3 plus CD2 or CD28, respectively, is important for the activation of human peripheral blood T lymphocytes (PBT). Mass spectrometry and site-directed mutagenesis revealed that Ser5 represents the only phospho-acceptor site of L-plastin in PBT. Wild-type L-plastin (wt-LPL) and a non-phosphorylatable 5A-L-plastin (5A-LPL) equally relocalized to the immunological synapse between PBT and APC. Yet importantly, cells expressing 5A-LPL showed a significantly lower expression of the T cell activation molecules CD25 and CD69 on the cell surface than cells expressing wt-LPL. This effect is due to a failure in the transport of CD25 and CD69 to the cell surface since the total amount of these proteins within the cells remained unchanged. In conclusion, phosphorylation of the actin bundling protein L-plastin represents a so-far-unknown mechanism by which costimulation controls the transport of activation receptors to the T cell surface.
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PMID:Costimulation induced phosphorylation of L-plastin facilitates surface transport of the T cell activation molecules CD69 and CD25. 1729 3

Hematopoietic growth factors (HGF) mobilize potential tolerogenic cells in transplant donors. Fms-like tyrosine kinase 3 ligand (Flt3L) mobilizes stem cells and dendritic cells (DCs) in human and nonhuman primate blood. Blood and renal and liver biopsies were obtained from untreated and Flt3L-mobilized rhesus macaques. Flt3L increased the number of myeloid CD11c(hi) and plasmacytoid CD123(hi) precursors in blood and both myeloid CD11c(+) HLA-DR(+) fascin(+) (CD45RA(-)) DCs and putative plasmacytoid CD11c(lo) CD45RA(hi) DC precursors in liver and kidneys, without affecting organ function. DC in Flt3L-treated monkeys were concentrated in the glomeruli and interstitium of kidneys, and in the portal triads and parenchyma of liver. These DCs exhibited the phenotype of immature antigen-presenting cells (APCs; CD83(-) CD86(lo) CCR5(+) CCR7(-)). HGF-induced changes reversed significantly within 7 days of Flt3L withdrawal. Therapeutic protocols that mobilize donor hematopoietic cells should consider the influence of HGF on the APC constituency of prospective organ allografts.
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PMID:Growth factor-induced mobilization of dendritic cells in kidney and liver of rhesus macaques: implications for transplantation. 1735 90

A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key role during mitotic exit.
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PMID:Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1). 2285 63