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Gene Review

RRAD  -  Ras-related associated with diabetes

Homo sapiens

Synonyms: GTP-binding protein RAD, RAD, RAD1, REM3, Ras associated with diabetes
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Disease relevance of RRAD

  • Whereas the standard immunosuppressive agents foster development of posttransplant lymphoproliferative disorders (PTLDs), the impact of RAD, a macrolide with potent immunosuppressive properties, and other immunosuppressive macrolides on these disorders remains undetermined [1].
  • We found that RAD had a profound inhibitory effect on in vitro growth of six different PTLD-like Epstein-Barr virus+ lymphoblastoid B cell lines [1].
  • In this study, we provide evidence that RAD has profound antiproliferative activity in vitro and in NOD/SCID mice in vivo against Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells [2].
  • None of the three RAD genes demonstrated somatic mutations in breast cancer cell lines [3].
  • CONCLUSION: SDZ RAD, in the absence of any other immunosuppressant and at doses that do not show any overt toxicity, considerably prolongs rejection-free survival of cynomolgus monkeys after life-supporting kidney allotransplantation [4].

Psychiatry related information on RRAD

  • EMG voluntary activity was recorded from both masseter muscles by means of coaxial needle electrodes before and after the electrical stimulation of MED and/or RAD at intensities below pain threshold [5].
  • Case descriptions of patients with probable Alzheimer's disease (AD) who were reliably classified into three neuropsychological subgroups (global [GAD], right-hemisphere [RAD], and left-hemisphere [LAD]) in an earlier cluster analytic study (Fisher et al., 1996) are presented [6].

High impact information on RRAD


Chemical compound and disease context of RRAD


Biological context of RRAD

  • However, an excess of minor alleles, all belonging to class I, II, or IV, was observed among NIDDM chromosomes (P < 0.025), suggesting a possible association between RAD1 and NIDDM predisposition [10].
  • The polymorphism, designated RAD1, consists of a variable number of trinucleotide repeats (GTT and ATT) located in the poly(A) region of an intronic Alu sequence [10].
  • RAD1 allele frequencies were determined in 210 NIDDM patients and 133 nondiabetic control subjects, all Caucasians [10].
  • Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe [11].
  • Both the RGE-VN and RAD-VN recombinant mutant proteins showed complete loss of cell adhesion activity, regardless of the receptor [12].

Anatomical context of RRAD

  • RGD peptides but not control RAD peptides disrupted the integrity of sprouting capillary-like structures and induced detachment of outgrowing endothelial cells cultured on top of collagen gels, but did not inhibit primary outgrowth of endothelial cells [13].
  • In contrast to the latter, SDZ RAD inhibits growth factor-driven cell proliferation in general, as demonstrated for the in vitro cell proliferation of a lymphoid cell line and of vascular smooth muscle cells [14].
  • RAD and SAD are very active in priming superoxides in the presence of microsomal enzymes as well as in inhibiting the synthesis of DNA and the growth of human colon tumor HT-29 cells in vitro [15].
  • We report the reference database for SOS at the radius (RAD), tibia (TIB), metatarsus (MTR) and phalanx (PLX) [16].
  • In addition to their individual effects, treatment with both RAD and LY294002 decreased serum-induced fibroblast proliferation and DNA synthesis significantly more than either drug alone [17].

Associations of RRAD with chemical compounds

  • As compared with the basal values cisapride significantly (P less than 0005, Wilcoxon Test) reduced the % RRAD from 45 min. after intake of the meal on wards [18].
  • However, the RGD site does not appear to be the binding site for alpha 9 beta 1, as the attachment of alpha 9 transfectants to this fragment was not inhibited by RGD peptide, nor by changing the RGD site to RAD or RAA [19].
  • Density-functional theory (DFT) and ab initio (QCISD and CBS-RAD) calculations suggest that complexation of "naked" lithium cations to olefins favors the addition of alkyl radicals to the double bond over abstraction of an allyllic hydrogen atom [20].
  • CONCLUSIONS: In combination with Neoral and corticosteroids, RAD doses of 2 mg and 4 mg/day resulted in lower rates of acute rejection episodes and efficacy failure than the 1 mg/day dose and were significantly more effective in reducing the severity of rejection [21].
  • In this group the MTL for cyclosporin was 143+/-13 and for RAD 38+/-3.Staggered treatment completely prevented rejection in four of six grafts [22].

Analytical, diagnostic and therapeutic context of RRAD

  • The genotype distribution was also analyzed by structural classes of the RAD1 polymorphism, and no difference was detected between the NIDDM and control groups [23].
  • In de novo liver transplant recipients, the overall extent of RAD absorption was not influenced by bile diversion, administration route, or time of administration [24].
  • Maintenance immunosuppression was with RAD (everolimus) (0.075 mg/kg per day administered subcutaneously) and FTY720 (0.3 mg/kg per day administered orally), both administered on day -2 through day 180 posttransplant [25].
  • RAD in de novo renal transplantation: comparison of three doses on the incidence and severity of acute rejection [21].
  • METHODS: Twenty-six de novo liver allograft recipients were assigned to one of four treatment groups based on the presence or absence of a T tube, administration route (nasogastric or nasoduodenal), and timing of RAD administration [24].


  1. The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. Majewski, M., Korecka, M., Kossev, P., Li, S., Goldman, J., Moore, J., Silberstein, L.E., Nowell, P.C., Schuler, W., Shaw, L.M., Wasik, M.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Jundt, F., Raetzel, N., Müller, C., Calkhoven, C.F., Kley, K., Mathas, S., Lietz, A., Leutz, A., Dörken, B. Blood (2005) [Pubmed]
  3. Common nonsense mutations in RAD52. Bell, D.W., Wahrer, D.C., Kang, D.H., MacMahon, M.S., FitzGerald, M.G., Ishioka, C., Isselbacher, K.J., Krainer, M., Haber, D.A. Cancer Res. (1999) [Pubmed]
  4. Oral efficacy of the macrolide immunosuppressant SDZ RAD and of cyclosporine microemulsion in cynomolgus monkey kidney allotransplantation. Schuurman, H.J., Ringers, J., Schuler, W., Slingerland, W., Jonker, M. Transplantation (2000) [Pubmed]
  5. Non-nociceptive upper limb afferents modulate masseter muscle EMG activity in man. Deriu, F., Milia, M., Sau, G., Podda, M.V., Ortu, E., Chessa, G., Aiello, I., Tolu, E. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2002) [Pubmed]
  6. Unmasking the heterogeneity of Alzheimer's disease: case studies of individuals from distinct neuropsychological subgroups. Fisher, N.J., Rourke, B.P., Bieliauskas, L.A., Giordani, B., Berent, S., Foster, N.L. Journal of clinical and experimental neuropsychology : official journal of the International Neuropsychological Society. (1997) [Pubmed]
  7. Targeting apoptosis pathways in cancer therapy. Ghobrial, I.M., Witzig, T.E., Adjei, A.A. CA: a cancer journal for clinicians. (2005) [Pubmed]
  8. Measurement of spontaneous and therapeutic agent-induced apoptosis with BCL-2 protein expression in acute myeloid leukemia. Banker, D.E., Groudine, M., Norwood, T., Appelbaum, F.R. Blood (1997) [Pubmed]
  9. Long-term results of treatment with mild toxicities in small cell lung carcinoma. Shirato, H., Tsujii, H., Miyamoto, H., Irie, G. Radiation medicine. (1986) [Pubmed]
  10. Trinucleotide repeats at the rad locus. Allele distributions in NIDDM and mapping to a 3-cM region on chromosome 16q. Doria, A., Caldwell, J.S., Ji, L., Reynet, C., Rich, S.S., Weremowicz, S., Morton, C.C., Warram, J.H., Kahn, C.R., Krolewski, A.S. Diabetes (1995) [Pubmed]
  11. Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe. MacInnes, M.A., Dickson, J.A., Hernandez, R.R., Learmonth, D., Lin, G.Y., Mudgett, J.S., Park, M.S., Schauer, S., Reynolds, R.J., Strniste, G.F. Mol. Cell. Biol. (1993) [Pubmed]
  12. Site-directed mutagenesis of the arginine-glycine-aspartic acid in vitronectin abolishes cell adhesion. Cherny, R.C., Honan, M.A., Thiagarajan, P. J. Biol. Chem. (1993) [Pubmed]
  13. Tensional forces in fibrillar extracellular matrices control directional capillary sprouting. Korff, T., Augustin, H.G. J. Cell. Sci. (1999) [Pubmed]
  14. SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo. Schuler, W., Sedrani, R., Cottens, S., Häberlin, B., Schulz, M., Schuurman, H.J., Zenke, G., Zerwes, H.G., Schreier, M.H. Transplantation (1997) [Pubmed]
  15. New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice. Sengupta, S.K., Kogan, Y., Kelly, C., Szabo, J. J. Med. Chem. (1988) [Pubmed]
  16. Reference database for bone speed of sound measurement by a novel quantitative multi-site ultrasound device. Weiss, M., Ben-Shlomo, A.B., Hagag, P., Rapoport, M. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2000) [Pubmed]
  17. Role of the phosphatidylinositol 3-kinase and mTOR pathways in the regulation of renal fibroblast function and differentiation. Winbanks, C.E., Grimwood, L., Gasser, A., Darby, I.A., Hewitson, T.D., Becker, G.J. Int. J. Biochem. Cell Biol. (2007) [Pubmed]
  18. Acute effect of the gastrokinetics cisapride and metoclopramide on the gastric emptying function in patients with the early satiety syndrome. Ghigliani, M., Iantorno, G., Vázquez, S., Varela, A. Acta gastroenterologica Latinoamericana. (1987) [Pubmed]
  19. The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin. Yokosaki, Y., Palmer, E.L., Prieto, A.L., Crossin, K.L., Bourdon, M.A., Pytela, R., Sheppard, D. J. Biol. Chem. (1994) [Pubmed]
  20. Lithium cation as radical-polymerization catalyst. Clark, T. J. Am. Chem. Soc. (2006) [Pubmed]
  21. RAD in de novo renal transplantation: comparison of three doses on the incidence and severity of acute rejection. Kahan, B.D., Kaplan, B., Lorber, M.I., Winkler, M., Cambon, N., Boger, R.S. Transplantation (2001) [Pubmed]
  22. Combined immunosuppression with cyclosporine (neoral) and SDZ RAD in non-human primate lung transplantation: systematic pharmacokinetic-based trials to improve efficacy and tolerability. Hausen, B., Ikonen, T., Briffa, N., Berry, G.J., Christians, U., Robbins, R.C., Hook, L., Serkova, N., Benet, L.Z., Schuler, W., Morris, R.E. Transplantation (2000) [Pubmed]
  23. Polymorphism at the rad gene is not associated with NIDDM in Finns. Orho, M., Carlsson, M., Kanninen, T., Groop, L.C. Diabetes (1996) [Pubmed]
  24. Pharmacokinetics and tolerability of 40-0-[2-hydroxyethyl]rapamycin in de novo liver transplant recipients. Levy, G.A., Grant, D., Paradis, K., Campestrini, J., Smith, T., Kovarik, J.M. Transplantation (2001) [Pubmed]
  25. Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD, and FTY720. Wijkstrom, M., Kenyon, N.S., Kirchhof, N., Kenyon, N.M., Mullon, C., Lake, P., Cottens, S., Ricordi, C., Hering, B.J. Transplantation (2004) [Pubmed]
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