We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Poly-ADP-ribosylation in health and disease.
- Authors
Masutani, M.; Nakagama, H.; Sugimura, T.
- Abstract
Carcinogenesis involves multiple steps and pathways with functional alterations in a variety of genes. There is accumulating evidence that a deficiency of poly(ADP-ribose) polymerase(PARP)-1leads to DNA repair defects, genomic instability, failure of induction of cell death and modulation of gene transcription.PARP-1also supports the growth of tumor cells in certain situations. Genetic analyses of thePARP-1gene have demonstrated alterations in neoplasms, and a mutation affecting the conserved amino acid E251 in germ cell tumors, as well as an association of a single-nucleotide polymorphism V762A with risk of prostate cancer. Recent development of a selective inhibitor of poly(ADP-ribose) glycohydrolase (PARG), the enzyme primarily responsible for degradation of poly(ADP-ribose), andPARG-deficient animals should facilitate studies of the relationship of poly(ADP-ribose) with carcinogenesis. Inhibitors of PARP have also suggested roles in the pathogenesis of autoimmune disease, and a promoter haplotype ofPARP-1confers a higher risk of rheumatoid arthritis. Further analysis ofPARP-1,PARGand otherPARPfamily genes should extend our understanding of the pathogenesis of cancer and autoimmune diseases. Furthermore, there is potential for sensitization to chemo- and radiation therapy of cancers as well as the treatment of autoimmune disease with development of stronger PARP inhibitors.
- Subjects
POST-translational modification; CANCER; AUTOIMMUNE diseases; CARCINOGENESIS; CELL death; RADIOTHERAPY
- Publication
Cellular & Molecular Life Sciences, 2005, Vol 62, Issue 7/8, p769
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-004-4509-x