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Gene Review

Parp1  -  poly (ADP-ribose) polymerase family, member 1

Mus musculus

Synonyms: 5830444G22Rik, ADP-ribosyltransferase diphtheria toxin-like 1, ADPRT 1, AI893648, ARTD1, ...
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Disease relevance of Parp1


High impact information on Parp1

  • Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP-/- mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin [5].
  • Our results identify NAD+ depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction, and provide information for the development of strategies to prevent the progression or manifestation of the disease in individuals at risk of developing type 1 diabetes [5].
  • Although PARP is specifically cleaved during apoptosis, cells lacking this molecule apoptosed normally in response to treatment with anti-Fas, tumor neurosis factor alpha, gamma-irradiation, and dexamethasone, indicating that PARP is dispensable in apoptosis and that PARP-/- thymocytes are not hypersensitive to ionizing radiation [6].
  • Whereas embryonic fibroblasts lacking PARP exhibit normal DNA excision repair, they grow more slowly in vitro [6].
  • PARP is important for genomic stability but dispensable in apoptosis [6].

Chemical compound and disease context of Parp1


Biological context of Parp1


Anatomical context of Parp1


Associations of Parp1 with chemical compounds


Physical interactions of Parp1


Enzymatic interactions of Parp1

  • We found that centrosomal p53 is poly(ADP-ribosyl)ated in vivo and centrosomal PARP-1 directly catalyzes poly(ADP-ribosyl)ation of p53 in vitro [15].
  • RB58-induced cytotoxicity was not inhibited by addition of the pan-caspase inhibitor zVAD, and Western blot analyses of RB58-infected HeLa cells indicated that neither caspase 3 nor 7 was cleaved and PARP remained in its full-length active form [23].
  • Blockade of caspase activity by Z-VAD reduced the amount of cleaved PARP-1 in fibroblasts [24].

Regulatory relationships of Parp1


Other interactions of Parp1

  • The abrogation of the oxydated status of p53(-/-) cells, due to the absence of parp-1, may be the cause of the delay in the onset of tumorigenesis in parp-1(-/-)p53(-/-) mice [12].
  • Interestingly, more than 58% of misregulated genes identified in double mutant cells were not altered in cells with either the Wrn or PARP-1 mutation alone [14].
  • Additional biochemical and immunocytochemical studies indicated that of several DNA repair enzymes investigated, only PARP was increased in scid mice, possibly in response to elevated DNA strand breaks [27].
  • Poly(ADP-ribose) polymerase-1 (PARP-1) and nuclear factor kappaB (NF-kappaB) have both been demonstrated to play a pathophysiological role in a number of inflammatory disorders [21].
  • We investigated the role of PARP-1 on the AP-1 pathway, which is involved in the signal transduction of the inflammatory process [20].
  • Haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer [28].

Analytical, diagnostic and therapeutic context of Parp1

  • In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen [29].
  • Mice genetically deficient of PARP-1 (PARP-1(-/-) mice) exhibited a significant reduction of myocardial damage after occlusion and reperfusion of the left anterior descending branch of the coronary artery compared with their wild-type littermates [30].
  • Poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme activated in response to DNA strand breaks, has been implicated in cell dysfunction in myocardial reperfusion injury [30].
  • Microarray analysis revealed that expression of several AP-1-dependent genes of proinflammatory mediators and HSPs was altered in PARP-1(-/-) mice [30].
  • CONCLUSION: Low-dose radiosensitization of actively dividing tumor cells by PARP-1 inhibitors suggests that they may have a role in enhancing the efficacy of ultrafractionated or low-dose-rate radiotherapy regimens [2].


  1. Poly(ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD+ depletion and mitochondrial permeability transition. Alano, C.C., Ying, W., Swanson, R.A. J. Biol. Chem. (2004) [Pubmed]
  2. PARP-1, PARP-2, and the cellular response to low doses of ionizing radiation. Chalmers, A., Johnston, P., Woodcock, M., Joiner, M., Marples, B. Int. J. Radiat. Oncol. Biol. Phys. (2004) [Pubmed]
  3. Effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, in a mouse model of acute pancreatitis induced by cerulein. Mazzon, E., Genovese, T., Di Paola, R., Mui??, C., Crisafulli, C., Malleo, G., Esposito, E., Meli, R., Sessa, E., Cuzzocrea, S. Eur. J. Pharmacol. (2006) [Pubmed]
  4. Expression of histone acetyltransferases was down-regulated in poly(ADP-ribose) polymerase-1-deficient murine cells. Ota, K., Kameoka, M., Tanaka, Y., Itaya, A., Yoshihara, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  5. Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Burkart, V., Wang, Z.Q., Radons, J., Heller, B., Herceg, Z., Stingl, L., Wagner, E.F., Kolb, H. Nat. Med. (1999) [Pubmed]
  6. PARP is important for genomic stability but dispensable in apoptosis. Wang, Z.Q., Stingl, L., Morrison, C., Jantsch, M., Los, M., Schulze-Osthoff, K., Wagner, E.F. Genes Dev. (1997) [Pubmed]
  7. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Yu, S.W., Wang, H., Poitras, M.F., Coombs, C., Bowers, W.J., Federoff, H.J., Poirier, G.G., Dawson, T.M., Dawson, V.L. Science (2002) [Pubmed]
  8. Teratogen-induced cell death in postimplantation mouse embryos: differential tissue sensitivity and hallmarks of apoptosis. Mirkes, P.E., Little, S.A. Cell Death Differ. (1998) [Pubmed]
  9. The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders. Hassa, P.O., Hottiger, M.O. Cell. Mol. Life Sci. (2002) [Pubmed]
  10. Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents. Pacher, P., Cziráki, A., Mabley, J.G., Liaudet, L., Papp, L., Szabó, C. Biochem. Pharmacol. (2002) [Pubmed]
  11. Local Administration of the Poly ADP-Ribose Polymerase (PARP) Inhibitor, PJ34 During Hindlimb Ischemia Modulates Skeletal Muscle Reperfusion Injury. Conrad, M.F., Albadawi, H., Stone, D.H., Crawford, R.S., Entabi, F., Watkins, M.T. J. Surg. Res. (2006) [Pubmed]
  12. Loss of poly(ADP-ribose) polymerase-1 causes increased tumour latency in p53-deficient mice. Conde, C., Mark, M., Oliver, F.J., Huber, A., de Murcia, G., Ménissier-de Murcia, J. EMBO J. (2001) [Pubmed]
  13. Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs. Espejel, S., Klatt, P., Ménissier-de Murcia, J., Martín-Caballero, J., Flores, J.M., Taccioli, G., de Murcia, G., Blasco, M.A. J. Cell Biol. (2004) [Pubmed]
  14. In vivo misregulation of genes involved in apoptosis, development and oxidative stress in mice lacking both functional Werner syndrome protein and poly(ADP-ribose) polymerase-1. Deschênes, F., Massip, L., Garand, C., Lebel, M. Hum. Mol. Genet. (2005) [Pubmed]
  15. Involvement of poly(ADP-Ribose) polymerase 1 and poly(ADP-Ribosyl)ation in regulation of centrosome function. Kanai, M., Tong, W.M., Sugihara, E., Wang, Z.Q., Fukasawa, K., Miwa, M. Mol. Cell. Biol. (2003) [Pubmed]
  16. Inhibition of poly(ADP-ribose) polymerase modulates tumor-related gene expression, including hypoxia-inducible factor-1 activation, during skin carcinogenesis. Martin-Oliva, D., Aguilar-Quesada, R., O'valle, F., Muñoz-Gámez, J.A., Martínez-Romero, R., García Del Moral, R., Ruiz de Almodóvar, J.M., Villuendas, R., Piris, M.A., Oliver, F.J. Cancer Res. (2006) [Pubmed]
  17. Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest after DNA methylating agent exposure. Horton, J.K., Stefanick, D.F., Naron, J.M., Kedar, P.S., Wilson, S.H. J. Biol. Chem. (2005) [Pubmed]
  18. Poly(ADP-ribose) polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9-mediated neuron death. Kauppinen, T.M., Swanson, R.A. J. Immunol. (2005) [Pubmed]
  19. Critical role of the automodification of poly(ADP-ribose) polymerase-1 in nuclear factor-kappaB-dependent gene expression in primary cultured mouse glial cells. Nakajima, H., Nagaso, H., Kakui, N., Ishikawa, M., Hiranuma, T., Hoshiko, S. J. Biol. Chem. (2004) [Pubmed]
  20. Poly(ADP-ribose) polymerase-1 regulates activation of activator protein-1 in murine fibroblasts. Andreone, T.L., O'Connor, M., Denenberg, A., Hake, P.W., Zingarelli, B. J. Immunol. (2003) [Pubmed]
  21. Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription. Hassa, P.O., Haenni, S.S., Buerki, C., Meier, N.I., Lane, W.S., Owen, H., Gersbach, M., Imhof, R., Hottiger, M.O. J. Biol. Chem. (2005) [Pubmed]
  22. Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1. Dantzer, F., de La Rubia, G., Ménissier-De Murcia, J., Hostomsky, Z., de Murcia, G., Schreiber, V. Biochemistry (2000) [Pubmed]
  23. Bordetella type III secretion induces caspase 1-independent necrosis. Stockbauer, K.E., Foreman-Wykert, A.K., Miller, J.F. Cell. Microbiol. (2003) [Pubmed]
  24. Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury. Pagano, A., Pitteloud, C., Reverdin, C., Métrailler-Ruchonnet, I., Donati, Y., Barazzone Argiroffo, C. Am. J. Respir. Cell Mol. Biol. (2005) [Pubmed]
  25. Decreased PARP-1 levels accelerate embryonic lethality but attenuate neuronal apoptosis in DNA polymerase beta-deficient mice. Sugo, N., Niimi, N., Aratani, Y., Masutani, M., Suzuki, H., Koyama, H. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  26. Transcription regulation of TNF-alpha-early response genes by poly(ADP-ribose) polymerase-1 in murine heart endothelial cells. Carrillo, A., Monreal, Y., Ramírez, P., Marin, L., Parrilla, P., Oliver, F.J., Yélamos, J. Nucleic Acids Res. (2004) [Pubmed]
  27. Elevated DNA double strand breaks and apoptosis in the CNS of scid mutant mice. Vemuri, M.C., Schiller, E., Naegele, J.R. Cell Death Differ. (2001) [Pubmed]
  28. Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality. Wang, X., Liu, L., Montagna, C., Ried, T., Deng, C.X. Cell Death Differ. (2007) [Pubmed]
  29. Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia. Martín-Oliva, D., O'Valle, F., Muñoz-Gámez, J.A., Valenzuela, M.T., Nuñez, M.I., Aguilar, M., Ruiz de Almodóvar, J.M., Garcia del Moral, R., Oliver, F.J. Oncogene (2004) [Pubmed]
  30. Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase-1. Zingarelli, B., Hake, P.W., O'Connor, M., Denenberg, A., Wong, H.R., Kong, S., Aronow, B.J. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
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