Prkdc

Summary

Gene Symbol: Prkdc
Description: protein kinase, DNA activated, catalytic polypeptide
Alias: AI326420, AU019811, DNA-PKcs, DNAPDcs, DNAPK, DNPK1, DOXNPH, HYRC1, XRCC7, dxnph, p460, scid, slip, DNA-dependent protein kinase catalytic subunit, DNA-PK catalytic subunit, doxorubicin nephropathy, severe combined immunodeficiency
Species: mouse
Products:     Prkdc

Top Publications

  1. Schuler W, Weiler I, Schuler A, Phillips R, Rosenberg N, Mak T, et al. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986;46:963-72 pubmed
    ..No such abnormal rearrangements were detected in transformed tissues from control mice. The scid mutation may adversely affect the recombinase system catalyzing the assembly of antigen receptor genes in ..
  2. Babu S, Porte P, Klei T, Shultz L, Rajan T. Host NK cells are required for the growth of the human filarial parasite Brugia malayi in mice. J Immunol. 1998;161:1428-32 pubmed
    ..survival and development in different strains of mice with varying levels of NK cell activity reveal that NOD/LtSz-scid/scid and NOD/LtSz-scid/scid B2m(null) mice (with diminished to absent NK cell activity respectively), are ..
  3. Taccioli G, Amatucci A, Beamish H, Gell D, Xiang X, Torres Arzayus M, et al. Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity. Immunity. 1998;9:355-66 pubmed
    ..Although our DNA-PKcs defective mice closely resemble Scid mice, they differ by having elevated numbers of CD4+CD8+ thymocytes...
  4. Goytisolo F, Samper E, Edmonson S, Taccioli G, Blasco M. The absence of the dna-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang. Mol Cell Biol. 2001;21:3642-51 pubmed
    ..Here we show that, besides DNA repair, a role for DNA-PKcs is to protect telomeres, which in turn are essential for chromosomal stability. ..
  5. Yotsumoto S, Saegusa K, Aramaki Y. Endosomal translocation of CpG-oligodeoxynucleotides inhibits DNA-PKcs-dependent IL-10 production in macrophages. J Immunol. 2008;180:809-16 pubmed
    ..We show in this study that peritoneal macrophages from SCID mice having mutations in the catalytic subunit of DNA-protein kinase (DNA-PKcs) were almost completely defective in ..
  6. Ferguson B, Mansur D, Peters N, Ren H, Smith G. DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. elife. 2012;1:e00047 pubmed publisher
    ..well-established functions in the DNA repair and V(D)J recombination, hence loss of DNA-PK leads to severe combined immunodeficiency (SCID)...
  7. Kumar P, Ban H, Kim S, Wu H, Pearson T, Greiner D, et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell. 2008;134:577-86 pubmed publisher
    ..Moreover, scFvCD7-9R could deliver antiviral siRNAs to naive T cells in Hu-HSC mice and effectively suppress viremia in infected mice. Thus, siRNA therapy for HIV infection appears to be feasible in a preclinical animal model. ..
  8. Shultz L, Ishikawa F, Greiner D. Humanized mice in translational biomedical research. Nat Rev Immunol. 2007;7:118-30 pubmed
  9. Cosgun K, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, et al. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell. 2014;15:227-38 pubmed publisher
    ..Thus, we have found that the capacity of this Kit mutation to open up stem cell niches across species barriers has significant potential and broad applicability in human HSC research. ..
  10. Franco S, Murphy M, Li G, Borjeson T, Boboila C, Alt F. DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J Exp Med. 2008;205:557-64 pubmed publisher
    ..We also find that under specific activation conditions, DNA-PKcs(-/-) B cells with chromosomal breaks are eliminated or at least prevented from progressing to metaphase via a p53-dependent response. ..

Detail Information

Publications80

  1. Schuler W, Weiler I, Schuler A, Phillips R, Rosenberg N, Mak T, et al. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986;46:963-72 pubmed
    ..No such abnormal rearrangements were detected in transformed tissues from control mice. The scid mutation may adversely affect the recombinase system catalyzing the assembly of antigen receptor genes in ..
  2. Babu S, Porte P, Klei T, Shultz L, Rajan T. Host NK cells are required for the growth of the human filarial parasite Brugia malayi in mice. J Immunol. 1998;161:1428-32 pubmed
    ..survival and development in different strains of mice with varying levels of NK cell activity reveal that NOD/LtSz-scid/scid and NOD/LtSz-scid/scid B2m(null) mice (with diminished to absent NK cell activity respectively), are ..
  3. Taccioli G, Amatucci A, Beamish H, Gell D, Xiang X, Torres Arzayus M, et al. Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity. Immunity. 1998;9:355-66 pubmed
    ..Although our DNA-PKcs defective mice closely resemble Scid mice, they differ by having elevated numbers of CD4+CD8+ thymocytes...
  4. Goytisolo F, Samper E, Edmonson S, Taccioli G, Blasco M. The absence of the dna-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang. Mol Cell Biol. 2001;21:3642-51 pubmed
    ..Here we show that, besides DNA repair, a role for DNA-PKcs is to protect telomeres, which in turn are essential for chromosomal stability. ..
  5. Yotsumoto S, Saegusa K, Aramaki Y. Endosomal translocation of CpG-oligodeoxynucleotides inhibits DNA-PKcs-dependent IL-10 production in macrophages. J Immunol. 2008;180:809-16 pubmed
    ..We show in this study that peritoneal macrophages from SCID mice having mutations in the catalytic subunit of DNA-protein kinase (DNA-PKcs) were almost completely defective in ..
  6. Ferguson B, Mansur D, Peters N, Ren H, Smith G. DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. elife. 2012;1:e00047 pubmed publisher
    ..well-established functions in the DNA repair and V(D)J recombination, hence loss of DNA-PK leads to severe combined immunodeficiency (SCID)...
  7. Kumar P, Ban H, Kim S, Wu H, Pearson T, Greiner D, et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell. 2008;134:577-86 pubmed publisher
    ..Moreover, scFvCD7-9R could deliver antiviral siRNAs to naive T cells in Hu-HSC mice and effectively suppress viremia in infected mice. Thus, siRNA therapy for HIV infection appears to be feasible in a preclinical animal model. ..
  8. Shultz L, Ishikawa F, Greiner D. Humanized mice in translational biomedical research. Nat Rev Immunol. 2007;7:118-30 pubmed
  9. Cosgun K, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, et al. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell. 2014;15:227-38 pubmed publisher
    ..Thus, we have found that the capacity of this Kit mutation to open up stem cell niches across species barriers has significant potential and broad applicability in human HSC research. ..
  10. Franco S, Murphy M, Li G, Borjeson T, Boboila C, Alt F. DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J Exp Med. 2008;205:557-64 pubmed publisher
    ..We also find that under specific activation conditions, DNA-PKcs(-/-) B cells with chromosomal breaks are eliminated or at least prevented from progressing to metaphase via a p53-dependent response. ..
  11. Agliano A, Martin Padura I, Mancuso P, Marighetti P, Rabascio C, Pruneri G, et al. Human acute leukemia cells injected in NOD/LtSz-scid/IL-2Rgamma null mice generate a faster and more efficient disease compared to other NOD/scid-related strains. Int J Cancer. 2008;123:2222-7 pubmed publisher
    ..We studied the engraftment kinetics of AML and ALL cell lines and primary cells in 3 strains of NOD.CB17-Prkdc(scid) (NOD/scid, NS)-related mice (NOD.Cg-Prkdc(scid)B2m(tm1Unc)/J, abbreviated NOD/scid/beta2 null, NSB; and NOD...
  12. Read T, Fogarty M, Markant S, McLendon R, Wei Z, Ellison D, et al. Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma. Cancer Cell. 2009;15:135-47 pubmed publisher
    ..CD15 is also found in a subset of human medulloblastomas, and tumors expressing genes similar to those found in murine CD15(+) cells have a poorer prognosis. Thus, CD15 may represent an important marker for TPCs in medulloblastoma. ..
  13. Bonifazi P, Zelante T, D Angelo C, De Luca A, Moretti S, Bozza S, et al. Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal Immunol. 2009;2:362-74 pubmed publisher
    ..Ultimately, affecting the local Th17/Treg balance might likely be exploited by the fungus for either commensalism or pathogenicity. ..
  14. Coombes J, Siddiqui K, Arancibia Cárcamo C, Hall J, Sun C, Belkaid Y, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med. 2007;204:1757-64 pubmed
    ..These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine. ..
  15. Callen E, Jankovic M, Difilippantonio S, Daniel J, Chen H, Celeste A, et al. ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell. 2007;130:63-75 pubmed
    ..Silencing this checkpoint permits DNA ends produced by V(D)J recombination in a lymphoid precursor to serve as substrates for translocations with chromosomes subsequently damaged by other means in mature cells. ..
  16. Simpson Abelson M, Sonnenberg G, Takita H, Yokota S, Conway T, Kelleher R, et al. Long-term engraftment and expansion of tumor-derived memory T cells following the implantation of non-disrupted pieces of human lung tumor into NOD-scid IL2Rgamma(null) mice. J Immunol. 2008;180:7009-18 pubmed
    Non-disrupted pieces of primary human lung tumor implanted into NOD-scid IL2Rgamma(null) mice consistently result in successful xenografts in which tissue architecture, including tumor-associated leukocytes, stromal fibroblasts, and tumor ..
  17. Kiefer K, Oshinsky J, Kim J, Nakajima P, Bosma G, Bosma M. The catalytic subunit of DNA-protein kinase (DNA-PKcs) is not required for Ig class-switch recombination. Proc Natl Acad Sci U S A. 2007;104:2843-8 pubmed
    ..However, we reported earlier that CSR can readily occur in Ig transgenic SCID mice lacking DNA-dependent protein kinase (DNA-PK) activity, a critical enzymatic activity for V(D)J recombination...
  18. Callen E, Jankovic M, Wong N, Zha S, Chen H, Difilippantonio S, et al. Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes. Mol Cell. 2009;34:285-97 pubmed publisher
    ..Our experiments reveal a DNA-PKcs-dependent pathway that regulates DNA repair and activation of p53 in the absence of ATM. ..
  19. McDermott S, Eppert K, Lechman E, Doedens M, Dick J. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood. 2010;116:193-200 pubmed publisher
    The nonobese diabetic/severe combined immune deficiency (NOD-scid) xenotransplantation model is the "gold standard" for assaying human hematopoietic stem cell activity...
  20. Rybanska I, Ishaq O, Chou J, Prakash M, Bakhsheshian J, Huso D, et al. PARP1 and DNA-PKcs synergize to suppress p53 mutation and telomere fusions during T-lineage lymphomagenesis. Oncogene. 2013;32:1761-71 pubmed publisher
    ..Together, our findings uncover defective DSB repair leading to tumor suppressor inactivation and abnormal segregation of fused chromosomes as two novel mechanisms promoting tumorigenesis in thymocytes lacking PARP1 and DNA-PKcs. ..
  21. Liccardi G, Hartley J, Hochhauser D. EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment. Cancer Res. 2011;71:1103-14 pubmed publisher
    ..Our findings show that EGFR subcellular distribution can modulate DNA repair kinetics, with implications for design of EGFR-targeted combinational therapies. ..
  22. Takenaka K, Prasolava T, Wang J, Mortin Toth S, Khalouei S, Gan O, et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007;8:1313-23 pubmed
    ..With the nobese diabetic (NOD)-severe combined immunodeficiency (SCID) xenotransplantation model, we found that the NOD background allowed better hematopoietic ..
  23. Orsburn B, Escudero B, Prakash M, Gesheva S, Liu G, Huso D, et al. Differential requirement for H2AX and 53BP1 in organismal development and genome maintenance in the absence of poly(ADP)ribosyl polymerase 1. Mol Cell Biol. 2010;30:2341-52 pubmed publisher
    ..These findings have important implications for our understanding of the mechanisms whereby ATM-regulated DDR prevents human aging and cancer. ..
  24. Choi Y, Li H, Son M, Wang X, Fornsaglio J, Sobol R, et al. Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair. PLoS ONE. 2014;9:e86358 pubmed publisher
    ..In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER. ..
  25. Majeti R, Park C, Weissman I. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell. 2007;1:635-45 pubmed publisher
    ..Furthermore, we report the first prospective isolation of a population of candidate human multipotent progenitors, Lin-CD34+CD38-CD90-CD45RA- cord blood. ..
  26. Bozulic L, Surucu B, Hynx D, Hemmings B. PKBalpha/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival. Mol Cell. 2008;30:203-13 pubmed publisher
    ..Furthermore, this function is apparently restricted to the PKBalpha isoform. ..
  27. Luo X, Tarbell K, Yang H, Pothoven K, Bailey S, Ding R, et al. Dendritic cells with TGF-beta1 differentiate naive CD4+CD25- T cells into islet-protective Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A. 2007;104:2821-6 pubmed
    ..When cotransferred with diabetogenic cells into NOD scid recipients, T regs induced with DCs and TGF-beta1 prevent the development of diabetes...
  28. Maser R, WONG K, Sahin E, Xia H, Naylor M, Hedberg H, et al. DNA-dependent protein kinase catalytic subunit is not required for dysfunctional telomere fusion and checkpoint response in the telomerase-deficient mouse. Mol Cell Biol. 2007;27:2253-65 pubmed
  29. Brehm M, Racki W, Leif J, Burzenski L, Hosur V, Wetmore A, et al. Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2r? null mice is enhanced by transgenic expression of membrane-bound human SCF. Blood. 2012;119:2778-88 pubmed publisher
    ..in immunodeficient mice expressing mutations in the IL2-receptor common ? chain (IL2rg) gene, including NOD-scid IL2r?(null) (NSG) mice...
  30. Quintana E, Shackleton M, Sabel M, Fullen D, Johnson T, Morrison S. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593-8 pubmed publisher
    ..1-0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice...
  31. King M, Covassin L, Brehm M, Racki W, Pearson T, Leif J, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol. 2009;157:104-18 pubmed publisher
    Immunodeficient non-obese diabetic (NOD)-severe combined immune-deficient (scid) mice bearing a targeted mutation in the gene encoding the interleukin (IL)-2 receptor gamma chain gene (IL2rgamma(null)) engraft readily with human ..
  32. Calderon B, Suri A, Unanue E. In CD4+ T-cell-induced diabetes, macrophages are the final effector cells that mediate islet beta-cell killing: studies from an acute model. Am J Pathol. 2006;169:2137-47 pubmed
    ..5 T-cell clone was established. Transfer of activated BDC T cells into NOD.scid mice resulted in diabetes within a week, characterized by strong inflammatory reaction...
  33. Rooney S, Alt F, Sekiguchi J, Manis J. Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development. Proc Natl Acad Sci U S A. 2005;102:2471-5 pubmed
    ..We found that ATM/Artemis double-deficient mice were viable and born in normal Mendelian numbers. Therefore, we conclude that DNA-PKcs has Artemis-independent functions in CSR and normal development. ..
  34. Bailey S, Cornforth M, Ullrich R, Goodwin E. Dysfunctional mammalian telomeres join with DNA double-strand breaks. DNA Repair (Amst). 2004;3:349-57 pubmed
    ..b>Severe combined immunodeficiency (scid) is caused by a mutation in the catalytic subunit of DNA-dependent protein kinase (DNA-PK), an ..
  35. Bogue M, Jhappan C, Roth D. Analysis of variable (diversity) joining recombination in DNAdependent protein kinase (DNA-PK)-deficient mice reveals DNA-PK-independent pathways for both signal and coding joint formation. Proc Natl Acad Sci U S A. 1998;95:15559-64 pubmed
    ..To resolve this issue, we examined V(D)J recombination in DNA-PKcs-deficient (SLIP) mice...
  36. Morrison C, Smith G, Stingl L, Jackson S, Wagner E, Wang Z. Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesis. Nat Genet. 1997;17:479-82 pubmed
    ..Mutation of the gene for DNA-PK catalytic subunit (Prkdc) cases defective antigen receptor V(D)J recombination and arrests B- and T-lymphocyte development in severe ..
  37. Ramiro A, Jankovic M, Callen E, Difilippantonio S, Chen H, McBride K, et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature. 2006;440:105-9 pubmed
    ..Our findings reveal a pathway for surveillance and protection against AID-dependent DNA damage, leading to chromosomal translocations. ..
  38. Gao Y, Chaudhuri J, Zhu C, Davidson L, Weaver D, Alt F. A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination. Immunity. 1998;9:367-76 pubmed
    ..Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs. ..
  39. Gu Y, Seidl K, Rathbun G, Zhu C, Manis J, van der Stoep N, et al. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity. 1997;7:653-65 pubmed
    ..These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components. ..
  40. Sipley J, Menninger J, Hartley K, Ward D, Jackson S, Anderson C. Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. Proc Natl Acad Sci U S A. 1995;92:7515-9 pubmed
    ..This location is coincident with that of XRCC7, the gene that complements the DNA double-strand break repair and V(D)J recombination defects (where V is variable,..
  41. DiLorenzo T, Lieberman S, Takaki T, Honda S, Chapman H, Santamaria P, et al. During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities. Clin Immunol. 2002;105:332-41 pubmed
    ..NIT-1 cells represent an unlimited peptide source that will allow for the future isolation and sequencing of the novel multiple epitopes targeted early in the autoimmune response by pathogenic CD8(+) T cells. ..
  42. Rolink A, Melchers F, Andersson J. The SCID but not the RAG-2 gene product is required for S mu-S epsilon heavy chain class switching. Immunity. 1996;5:319-30 pubmed
    ..the capacity of precursor B cells from normal (BDF1) and V(D)J recombinase-deficient (RAG-27) or defective (SCID) mice to be induced by a CD40-specific monoclonal antibody and IL-4 to epsilon H chain gene transcription and to S ..
  43. Rogers H, Sheehan K, Brunt L, Dower S, Unanue E, Schreiber R. Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice. Proc Natl Acad Sci U S A. 1992;89:1011-5 pubmed
    Using T- and B-cell deficient C.B-17 mice with the scid mutation, we have previously documented the existence of a T-cell-independent but interferon gamma-dependent pathway of macrophage activation that confers upon the host partial ..
  44. Sekiguchi J, Ferguson D, Chen H, Yang E, Earle J, Frank K, et al. Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development. Proc Natl Acad Sci U S A. 2001;98:3243-8 pubmed
    ..Finally, in dramatic contrast to effects on Lig4 deficiency, ATM deficiency causes early embryonic lethality in Ku- or DNA-PKcs-deficient mice, providing evidence for an NHEJ-independent role for the DNA-PK holoenzyme. ..
  45. Biedermann K, Sun J, Giaccia A, Tosto L, Brown J. scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. Proc Natl Acad Sci U S A. 1991;88:1394-7 pubmed
    C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell ..
  46. Mosier D, Stell K, Gulizia R, Torbett B, Gilmore G. Homozygous scid/scid;beige/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation. J Exp Med. 1993;177:191-4 pubmed
    The autosomal recessive scid mutation results in defective immunoglobulin and T cell receptor gene rearrangement. The scid mutation occurred in the allotype congenic C.B-17 line, and up to 25% of C...
  47. Nacht M, Strasser A, Chan Y, Harris A, Schlissel M, Bronson R, et al. Mutations in the p53 and SCID genes cooperate in tumorigenesis. Genes Dev. 1996;10:2055-66 pubmed
    ..The severe combined immune deficiency (scid) focus encodes the catalytic subunit of DNA protein kinase (DNA-PKcs), a protein complex that has a role in the ..
  48. Stetson D, Medzhitov R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity. 2006;24:93-103 pubmed
    ..These findings define an innate immune response to DNA linked to type I interferon production. ..
  49. Manis J, Dudley D, Kaylor L, Alt F. IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells. Immunity. 2002;16:607-17 pubmed
    ..We conclude that DNA-PKcs is required for CSR to most C(H) genes but that CSR to gamma1 occurs via a DNA-PKcs-independent mechanism. ..
  50. Douglas P, Sapkota G, Morrice N, Yu Y, Goodarzi A, Merkle D, et al. Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase. Biochem J. 2002;368:243-51 pubmed
    ..Moreover, we show that DNA-PKcs is phosphorylated in vivo at Thr2609, Ser2612, Thr2638 and Thr2647 in okadaic acid-treated human cells. We propose that phosphorylation of these sites may play an important role in DNA-PK function. ..
  51. Espejel S, Franco S, Sgura A, Gae D, Bailey S, Taccioli G, et al. Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. EMBO J. 2002;21:6275-87 pubmed
    ..These results suggest a critical role of DNA-PKcs in both cancer and aging. ..
  52. Bailey S, Brenneman M, Halbrook J, Nickoloff J, Ullrich R, Goodwin E. The kinase activity of DNA-PK is required to protect mammalian telomeres. DNA Repair (Amst). 2004;3:225-33 pubmed
    ..These results indicate that the kinase activity of DNA-PK is crucial to reestablishing a protective terminal structure, specifically on telomeres replicated by leading-strand DNA synthesis. ..
  53. Battaglia M, Stabilini A, Draghici E, Migliavacca B, Gregori S, Bonifacio E, et al. Induction of tolerance in type 1 diabetes via both CD4+CD25+ T regulatory cells and T regulatory type 1 cells. Diabetes. 2006;55:1571-80 pubmed
    ..Rapamycin plus IL-10 treatment, promoting distinct subsets of Tr cells, may constitute a novel and potent tolerance-inducing protocol for immune-mediated diseases. ..
  54. Espejel S, Klatt P, Menissier de Murcia J, Martin Caballero J, Flores J, Taccioli G, et al. Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs. J Cell Biol. 2004;167:627-38 pubmed
    ..These results support the notion that absence of telomerase and short telomeres in combination with DNA repair deficiencies accelerate the aging process without impacting on tumorigenesis. ..
  55. Ishii K, Takeshita F, Gursel I, Gursel M, Conover J, Nussenzweig A, et al. Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation. J Exp Med. 2002;196:269-74 pubmed
    ..These results support a model in which CpG signaling is mediated through TLR-9 but not DNA-PK, and suggest that wortmannin-sensitive member(s) of the PI3-kinase family play a critical role in shuttling CpG DNA to TLR-9. ..
  56. Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood. 2005;106:1565-73 pubmed
    Here we report that a new nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine receptor gamma chain (NOD/SCID/interleukin 2 receptor [IL2r] gamma(null)) ..
  57. Bosma G, Custer R, Bosma M. A severe combined immunodeficiency mutation in the mouse. Nature. 1983;301:527-30 pubmed
    The most debilitating human lymphoid deficiency disease, known as severe combined immunodeficiency (SCID), impairs the differentiation of both T and B lymphocytes...
  58. Powrie F, Leach M, Mauze S, Menon S, Caddle L, Coffman R. Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity. 1994;1:553-62 pubmed
    We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RBhi subpopulation of CD4+ T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RBlo CD4+ T cell subset...
  59. Chang Y, Bosma G, Bosma M. Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination. Immunity. 1995;2:607-16 pubmed
    The inability of scid pro-B cells to progress to the pre-B and B cell stages is believed to be caused by a defective recombinase activity that fails to resolve chromosomal breaks resulting from attempted V(D)J recombination...
  60. Dudek N, Thomas H, Mariana L, Sutherland R, Allison J, Estella E, et al. Cytotoxic T-cells from T-cell receptor transgenic NOD8.3 mice destroy beta-cells via the perforin and Fas pathways. Diabetes. 2006;55:2412-8 pubmed
    ..Therefore, NOD8.3 T-cells use both perforin and Fas pathways to kill beta-cells and the surprising blockade of NOD8.3 T-cell-mediated beta-cell death by SOCS-1 overexpression may be due in part to reduced target cell recognition. ..
  61. Danska J, Holland D, Mariathasan S, Williams K, Guidos C. Biochemical and genetic defects in the DNA-dependent protein kinase in murine scid lymphocytes. Mol Cell Biol. 1996;16:5507-17 pubmed
    The scid gene product has been identified as the 460-kDa catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs p460), a member of the phosphatidylinositol 3-kinase family...
  62. Shultz L, Schweitzer P, Christianson S, Gott B, Schweitzer I, Tennent B, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol. 1995;154:180-91 pubmed
    The scid mutation was backcrossed ten generations onto the NOD/Lt strain background, resulting in an immunodeficient stock (NOD/LtSz-scid/scid) with multiple defects in adaptive as well as nonadaptive immunologic function...
  63. Bogue M, Zhu C, Aguilar Cordova E, Donehower L, Roth D. p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Genes Dev. 1996;10:553-65 pubmed
    The murine scid mutation affects both V(D)J recombination and DNA repair...
  64. Gu Y, Sekiguchi J, Gao Y, Dikkes P, Frank K, Ferguson D, et al. Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice. Proc Natl Acad Sci U S A. 2000;97:2668-73 pubmed
    ..We conclude that normal development of the nervous system depends on the four evolutionarily conserved nonhomologous DNA end joining factors. ..
  65. Gurley K, Kemp C. Synthetic lethality between mutation in Atm and DNA-PK(cs) during murine embryogenesis. Curr Biol. 2001;11:191-4 pubmed
    ..b>Prkdc(scid/scid) mice have a homozygous mutation in the gene encoding DNA-PK(cs) and, like Atm(-/-) mice, are viable and ..
  66. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100:3175-82 pubmed
    ..animal recipient for xenotransplantation, NOD/SCID/gamma(c)(null) mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rgamma (IL-2Rgamma) allelic mutation (gamma(c)(null)) were generated ..
  67. Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, et al. Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood. 2003;102:873-80 pubmed
    ..We report ontogenic, functional, and histologic examination results of reconstituted human lymphocytes in NOD/SCID/ gammacnull mice after the transplantation of human cord blood (CB) CD34+ cells...
  68. Graser R, DiLorenzo T, Wang F, Christianson G, Chapman H, Roopenian D, et al. Identification of a CD8 T cell that can independently mediate autoimmune diabetes development in the complete absence of CD4 T cell helper functions. J Immunol. 2000;164:3913-8 pubmed
    ..develop IDDM at a greatly accelerated rate when residual CD4 helper T cells were eliminated by introduction of the scid mutation or a functionally inactivated CD4 allele...
  69. Bosma G, Kim J, Urich T, Fath D, Cotticelli M, Ruetsch N, et al. DNA-dependent protein kinase activity is not required for immunoglobulin class switching. J Exp Med. 2002;196:1483-95 pubmed
    ..To test whether DNA-PKcs activity is essential for CSR, we examined whether IgM(+) B cells from scid mice with site-directed H and L chain transgenes were able to undergo CSR...
  70. Chang Y, Bosma M. Effect of different Ig transgenes on B cell differentiation in scid mice. Int Immunol. 1997;9:373-80 pubmed
    ..study we show that the ability of bone marrow pre-B cells to differentiate into B cells in H/L chain transgenic scid mice correlates with the ability of the transgenes to inhibit initiation of endogenous kappa gene rearrangement...
  71. Shultz L, Lyons B, Burzenski L, Gott B, Chen X, Chaleff S, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174:6477-89 pubmed
    ..report the development and characterization of a new genetic stock of IL-2R common gamma-chain deficient NOD/LtSz-scid (NOD-scid IL2Rgamma(null)) mice and document their ability to support human mobilized blood HSC engraftment and ..
  72. Dragoi A, Fu X, Ivanov S, Zhang P, Sheng L, Wu D, et al. DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA. EMBO J. 2005;24:779-89 pubmed
    ..Thus, our findings establish a novel role for DNA-PKcs in CpG-DNA signaling and define a CpG-DNA/DNA-PKcs/Akt pathway. ..