Chapter category: DNA
Functional Interactions of PARP-1With p53 Molecular Interactions of PARP-1 With p53
Poly(ADP-Ribosyl)ation
Edited by: Alexander BurkleISBN: 0-387-33371-1
» Get more information about this book at landesbioscience.com «
Chapter authors:
Rafael Alvarez-Gonzalez, Hanswalter Zentgraf, Manfred Frey and Hilda Mendoza-Alvarez
A close correlation between the frequency of specific mutations of oncogenes and/or tumor suppressor genes in mammals and cancer has been suspected for a long time. For instance, either spontaneous or forcefully inflicted mutations of a tumor suppressor gene coding for a protein known as p53 are usually associated with a variety of malignant tumors. Overwhelming experimental evidence indicates that more than 50% of human neoplasias1 contain one or multiple mutations in one or both alleles of p53. Therefore, the expression product of this pivotal gene, when mutated, appears to play a major role in carcinogenesis. Further significance of p53, as a tumor suppressor protein, is underscored by the fact that over 90% of all tumor-derived mutations associated with it, result in structural and/or functional alterations of its sequence-specific DNA-binding domain2 (Seq-Sp DBD, Fig. 1). Interestingly, the high mutation frequency observed with p53 in malignant tissues initially lead to the misidentification of a mutant of this chromosomal locus as an oncogene rather than its wild type version which functions as the opposite, a tumor suppressor product. An overwhelming amount of work has been done in the last few years to unveil the physiological, biochemical and molecular significance of p53, especially at the protein level. However, in this review the discussion centers on the relevance of the p53 structure and function relationships with poly(ADP-ribose) polymerase-1 (PARP-1), a prominent DNA-strand break sensor in higher eucaryotes, and the biochemical pathway of protein-poly(ADP-ribosyl)ation. A special emphasis is placed on how these two polypeptides work together in the maintenance of genomic integrity. Therefore, we will present the primary sequence and domain structure of both proteins first.
Additional chapters from this book:
Functional Interactions of PARP-1 with p53
Rafael Alvarez-Gonzalez, Hanswalter Zentgraf, Manfred Frey and Hilda Mendoza-Alvarez
A close correlation between the frequency of specific mutations of oncogenes and/or tumor suppressor genes in mammals and cancer has been suspected for a long time. For instance, either spontane...
Poly(ADP-ribose) Polymerase (PARP) and Excitotoxicity
Domenico E. Pellegrini-Giampietro, Alberto Chiarugi and Flavio Moroni
Neuronal injury resulting from glutamate receptor-mediated excitotoxicity has been implicated in a wide spectrum of neurological disorders. Following dramatic results in the preclinical setting, ant...
Functional Interactions of PARP-1With p53 Molecular Interactions of PARP-1 With p53
Rafael Alvarez-Gonzalez, Hanswalter Zentgraf, Manfred Frey and Hilda Mendoza-Alvarez
A close correlation between the frequency of specific mutations of oncogenes and/or tumor suppressor genes in mammals and cancer has been suspected for a long time. For instance, either spontaneous ...
Role of Poly-ADP-Ribosylation in Cancer Development
Mitsuko Masutani, Akemi Gunji, Masahiro Tsutsumi, Kumiko Ogawa, Nobuo Kamada, Tomoyuki Shirai, Kou-ichi Jishage, Hitoshi Nakagama and Takashi Sugimura
Elucidation of the relationship between poly-ADP-ribosylation and carcinogenesis has markedly progressed by the recent development of knockout or transgenic mice models of poly(ADP-ribose) polymeras...
Genome Degradation by DNAS1L3 Endonuclease: A Key PARP-1-Regulated Event in Apoptosis
A. Hamid Boulares, Alexander G. Yakovlev and Mark E. Smulson
Degradation of chromatin into internucleosomal fragments, a prevailing hallmark of apoptosis in most cells and tissues, has been tightly associated with a Ca2+ and Mg2+-dependent endonuclease activi...
Parp and Epigenetic Regulation
Paola Caiafa
In the post-genome era attention is being focused on those epigenetic modifications which modulate chromatin structure to guarantee that information present on DNA is read correctly and at the most ...
Dynamic Interaction between PARP-1, PCNA and p21waf1/cip1
Ennio Prosperi and A. Ivana Scovassi
Poly(ADP-ribose) polymerase (PARP-1) plays a crucial role in DNA repair and interacts with many DNA replication/repair factors, including the Proliferating Cell Nuclear Antigen (PCNA), a protein inv...
DNA Damage Signaling through Poly(ADP-Ribose)
Maria Malanga and Felix R. Althaus
Several lines of evidence reveal that poly(ADP-ribose)polymerase-1 (PARP-1) operates in a DNA damage signaling network. Poly(ADP-ribose) metabolism induced by DNA damage participates in DNA repair a...
PARP and the Release of Apoptosis-Inducing Factor from Mitochondria
Suk Jin Hong, Ted M. Dawson and Valina L. Dawson
Death is the inevitable fate for all living things including individual cells. However, untimely death results in dysfunction and disease. Understanding the normal regulation of cell death and cell ...
Poly(ADP-Ribosyl)ation and Aging
Sascha Beneke and Alexander Bürkle
In this Chapter, we review the evidence suggesting that the family of poly(ADP-ribose) polymerases (PARPs) is involved in regulation of the aging process. First, as genotoxic stress, mainly produced...
Targeting the Poly(ADP-Ribose) Glycohydrolase (PARG) Gene in Mammals
Ulrich Cortes and Zhao-Qi Wang
Poly(ADP-ribosyl)ation is a post-translational modification of proteins. Upon DNA damage, poly(ADP-ribose) polymerase-1 catalyzes the transfer of ADP-ribose moieties from NAD+ onto acceptor proteins...
Enzymes in Poly(ADP-Ribose) Metabolism
Ralph G. Meyer , Mirella L. Meyer-Ficca, Elaine L. Jacobson and Myron K. Jacobson
Studies over many years have revealed the central importance of poly(ADP-ribose) me tabolism in the maintenance of genomic integrity. While the involvement of poly(ADP-ribose) polymerase-1 (PARP-1) ...
PARP Inhibitors and Cancer Therapy
Nicola J. Curtin
The compelling evidence for the role of poly(ADP-ribose) polymerase(s) (PARP) in the cellular reaction to genotoxic stress was the stimulus to develop inhibitors as therapeu tic agents to potentiate...
Role of Poly (ADP-ribose) Polymerase Activation in the Pathogenesis of Inflammation and Circulatory Shock Poly (ADP-ribose) Polymerase and Shock and Inflammation
Csaba Szabo
Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Activation of PARP may dra matically lower the intracellula...
Poly(ADP-ribose) Polymerase and Ischemia-Reperfusion Injury
Prabal K. Chatterjee and Christoph Thiemermann
Poly (adenosine 5'-diphosphate ribose) polymerase-1 (PARP-1) is an abundant chromatin-bound enzyme which is present in the nuclei of most cells. The physiological role of PARP-1 involves its activat...
PARP-1 and the Shape of Cell Death
Laslo Virag
The following review discusses the mechanisms through which cell death may be regu lated by poly(ADP-ribose) polymerase-1(PARP-1), a nuclear enzyme that catalyzes the synthesis of long, branching (A...
NAD-metabolism and Regulatory Functions
Mathias Ziegler
Poly-ADP-ribosylation has turned out to be a major NAD-consuming process in most eukaryotic cells. Although PARP1 exhibits by far the highest capacity to synthesise poly-ADP-ribose, it is active onl...
PARP-1 As Novel Coactivator of NF-kB in Inflammatory Disorders
Paul O. Hassa and Michael O. Hottiger
Mammalian poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin associated protein and belongs to a large family of enzymes that can synthesize large branched polymers of ADP-ribose units b...
PARP-2: Structure-Function Relationship
Valérie Schreiber, Michelle Ricoul, Jean-Christophe Amé, Françoise Dantzer, Véronique Meder, Catherine Spenlehauer, Patrick Stiegler, Claude Niedergang, Laure Sabatier,Vincent Favaudon, Josiane Menissier-de Murcia and Gilbert de Murcia
Poly(ADP-ribosyl)ation is an immediate DNA damage-dependent posttranslational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Pol...
Roles of Poly(ADP-Ribose) Metabolism in the Regulation of Centrosome Duplication and in the Maintenance of Neuronal Integrity
Masanao Miwa, Masayuki Kanai, Masahiro Uchida, Kazuhiko Uchida and Shuji Hanai
The chemical structure of poly(ADP-ribose) suggests not only that its modification of acceptor proteins should modify the structure and function of the acceptor proteins, but also that the poly(ADP-...
