The PARP family: insights into functional aspects of poly (ADP‐ribose) polymerase‐1 in cell growth and survival

Abstract

PARP family members can be found spread across all domains and continue to be essential molecules from lower to higher eukaryotes. Poly (ADP-ribose) polymerase 1 (PARP-1), newly termed ADP-ribosyltransferase D-type 1 (ARTD1), is a ubiquitously expressed ADP-ribosyltransferase (ART) enzyme involved in key cellular processes such as DNA repair and cell death. This review assesses current developments in PARP-1 biology and activation signals for PARP-1, other than conventional DNA damage activation. Moreover, many essential functions of PARP-1 still remain elusive. PARP-1 is found to be involved in a myriad of cellular events via conservation of genomic integrity, chromatin dynamics and transcriptional regulation. This article briefly focuses on its other equally important overlooked functions during growth, metabolic regulation, spermatogenesis, embryogenesis, epigenetics and differentiation. Understanding the role of PARP-1, its multidimensional regulatory mechanisms in the cell and its dysregulation resulting in diseased states, will help in harnessing its true therapeutic potential.

The antiproliferative and apoptotic effects of apigenin on glioblastoma cells

“…Apigenin inhibited Bcl‐xL in both cell lines suggesting the possible involvement of cytochrome C and caspase‐9 activation in apigenin‐induced GBM apoptosis . PARP cleavage results in a loss of the DNA repair function . We showed marked increase in PARP cleavage at 40 and 80 μ m indicating a loss of DNA repair and G2/M cell cycle arrest.…”

“…[32] PARP cleavage results in a loss of the DNA repair function. [33] We showed marked increase in PARP cleavage at 40 and 80 lM indicating a loss of DNA repair and G2/M cell cycle arrest. We observed a G2/M phase cell cycle arrest with flow cytometry confirming the effect of apigenin on PARP inactivation.…”

Parent‐Metabolite Pharmacokinetic Modeling and Pharmacodynamics of Veliparib (ABT‐888), a PARP Inhibitor, in Patients With BRCA 1/2–Mutated Cancer or PARP‐Sensitive Tumor Types

“…Poly‐ADP‐ribose polymerase (PARP) is a nuclear enzyme that signals DNA damage and contributes to the maintenance of genomic integrity . After single‐ and double‐stranded DNA breaks, the catalytic domains of PARP are immediately activated to regulate DNA damage repair through the base excision repair pathway, Elevated levels of PARP in cancer cells compared with normal cells are recognized as one of the mechanisms by which tumor cells avoid apoptosis caused by DNA‐damaging agents .…”

“…8 In light of a strong rationale that veliparib can be developed as a monotherapy, a clinical study was conducted to evaluate the safety, tolerability, and PK of single-agent veliparib in patients with either BRCA 1/2-mutated cancer or PARP-sensitive tumors. The objectives of this analysis were (1) to characterize the population PK of veliparib and M8 and to assess the potential impact of intrinsic factors on the PK parameters, and (2) to explore the exposure-response relationship for PAR in PBMCs.…”

Poly(ADP‐ribose) polymerase‐1 (PARP‐1) regulates developmental morphogenesis and chemotaxis in Dictyostelium discoideum

“…Also, thick interrupted streams and smaller aggregates as seen in ADPRT1A KO cells (Figure A) were supported by the study that showed PDSA − cells to have unusually thick and transient streams at high cell densities [Garcia et al., ] and altered REGA levels [Wessels et al., ]. PARP‐1 has also been reported to be involved in regulating cellular differentiation [Pavri et al., ; Jubin et al., ]. The Dictyostelium developmental cycle exhibits cell differentiation into prespore and prestalk cells [Jeremyn et al., ].…”