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Epigenetic Modifications of Histones
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
George Rasti, Alejandro Vaquero
ADP-ribosylation (ADPR) involves the addition of the ADP-ribose moiety of NAD+. Some members of the PARP superfamily have been shown to promote mono- or poly-ADPR of histones. The levels of poly ADP-ribosylation, PARP-1, and PARP-2 catalytic activity (14), and the turnover of ADP-ribosyl residues all decreased during the differentiation of the germinal cell line, most noticeably at the end of spermiogenesis, which suggests a possible role for this modification in male fertility (15).
Poly (ADP-Ribose) Polymerase — A Nonhistone Nuclear Protein
Published in Lubomir S. Hnilica, Chromosomal Nonhistone Proteins, 2018
Since the discovery of poly (ADP-ribose) polymerase and ADP-ribosylation, many roles have been assigned to this reaction, yet the precise biological function for poly (ADP-ribose) is still not known. Functional roles for both include the maintenance of chromatin superstructure, regulation of DNA synthesis and DNA repair, cell multiplication, transformation, and differentiation.
Translation and Post-Translational Modifications During Aging
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
The structure and function of many proteins is modulated by posttranslational ADP-ribosylation, which is the enzymic addition of a ADP-ribose derived from NAD+. These proteins include the nuclear proteins topoisomerase I, DNA ligase II, endonuclease, histones H1, H2B, and H4, DNA polymerases α and β, and the cytoplasmic proteins adenyl cyclase and elongation factor EF-2.51,120–122 Generally, the cytoplasmic enzymes called mono-ADP-ribosyltransferases catalyze the formation of a mono-ADP-ribosyl protein, while the nuclear enzyme poly(ADP-ribose)polymerase (PARP) catalyzes the addition of several ADP-ribosyl residues to proteins.120,121 ADP-ribosylation of proteins is involved in various cellular processes such as the maintenance of chromatin structure, DNA repair, protein synthesis, cell differentiation, and cell transformation.121
GRP75 as a functional element of cholix transcytosis
Published in Tissue Barriers, 2023
Keyi Liu, Tom Hunter, Alistair Taverner, Kevin Yin, Julia MacKay, Kate Colebrook, Morgan Correia, Amandine Rapp, Randall J. Mrsny
Chx is a member of the toxin family that includes the diphtheria toxin produced by Corynebacterium diphtheriae and exotoxin A produced by Pseudomonas aeruginosa. All three proteins intoxicate mammalian cells by the enzymatic ADP-ribosylation of eukaryotic elongation factor 2 to induce apoptosis through the blockade of protein synthesis.8,9 The first 266 amino acid (domain I) of Chx are sufficient for successful completion of apical to basal (A→B) transcytosis across polarized intestinal epithelial cells and targeting of this toxic action to non-polarized cells within the lamina propria.10 In order to maintain systemic homeostasis and protect the body from toxic elements present in the diet or released by the microbiome, proteins absorbed at the surface of enterocytes via receptor-mediated endocytosis are typically either returned to the intestinal lumen or shuttled to a lysosomal degradation pathway. Since Chx appears to have identified a transcytosis process that avoids these fates,10 we wanted to better understand the cellular processes that allowed for this unusual outcome.
Olaparib@human serum albumin nanoparticles as sustained drug-releasing tumour-targeting nanomedicine to inhibit growth and metastasis in the mouse model of triple-negative breast cancer
Published in Journal of Drug Targeting, 2022
Nageswara Rao Vysyaraju, Milan Paul, Sanjay Ch, Balaram Ghosh, Swati Biswas
Poly(adenosine diphosphate-ribose) polymerase (PARP) family of proteins is vital to repairing breaks in DNA single strands [7]. The BRCA-mutated cells activate PARP enzymes, which enhance the process of ADP ribosylation. The repaired single-strand DNA replicates lead to the survival of the cells. PARPi inhibits PARP enzyme activity and forms single-stranded DNA (ssDNA), which eventually causes the double-stranded DNA (dsDNA) breakage at the replication fork [8]. However, the exact mechanism of enzyme inhibition by the small molecule PARP inhibitors is still unclear [9]. The BRCA1/2-mutated cells are sensitive to PARP inhibition to a much greater extent than the other breast cancer cells undergoing the BRCA-mediated HR mechanism for DNA repair [10]. Likewise, PARP-inhibition enhances the effectiveness of radiation therapy by inactivating the repair procedure of damaged DNAs accumulated following radiation treatment [11].
Poly (ADP-ribose) polymerase (PARP) as target for the treatment of epithelial ovarian cancer: what to know
Published in Expert Opinion on Investigational Drugs, 2021
Luigi Della Corte, Virginia Foreste, Claudia, Di Filippo, Pierluigi Giampaolino, Giuseppe Bifulco
The PARPs family share the ability to catalyze the transfer of ADP-ribose to target proteins (poly ADP-ribosylation) [34]. Several cellular substrates for PARP have been defined, and a majority of these proteins are nuclear proteins that are involved in nucleic acid metabolism, modulation of chromatin structure, DNA synthesis, and DNA repair [35]. PARP1 is the first and best-characterized member of the PARP family, while PARP2 has 69% similarity to PARP1 in its catalytic domain, and was identified based on the persistence of PARP activity in PARP1-deficient cells [36]. PARP-1 has a molecular weight of 113 kDa and consists of three major domains [37]: the DNA-binding domain which includes two zinc-finger motifs that bind to DNA breaks thus triggering enzyme activation, a centrally located 16 kDa auto-modification domain which contains conserved glutamate and lysine residues, the targets for auto-poly (ADP-ribosyl)ation, and the 55 kDa C-terminal catalytic domain, the region targeted by the majority of drug discovery programs [38].