Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1), also referred to as ADP-ribosyltransferase Diphtheria toxin-like 1 (ARTD1), is an abundant nuclear protein that plays key roles in a variety of nuclear processes, including the regulation of transcription. PARP-1 possesses an intrinsic enzymatic activity that catalyzes the transfer of ADP-ribose (ADPR) units from nicotinamide adenine dinucleotide (NAD+) onto target gene regulatory proteins, thereby modulating their activities. Although great strides have been made in the past decade in deciphering the seemingly opposing and varied roles of PARP-1 in gene regulation, many puzzles remain. In this review, we discuss the current state of understanding in this area, especially how PARP-1 interfaces with various components of gene regulatory pathways (e.g., the basal transcription machinery, DNA-binding transcription factors, coregulators, chromatin remodeling, histone modifications, and DNA methylation). In addition, we discuss some gene-specific, cell type-specific, and cell state-specific effects of PARP-1 on gene regulation, which might contribute to its biological functions. Finally, we review some of the recent progress targeting PARPs using chemical inhibitors, some of which may alter PARP-1-dependent gene regulatory programs to promote therapeutic outcomes.
Original language | English (US) |
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Pages (from-to) | 1109-1123 |
Number of pages | 15 |
Journal | Molecular aspects of medicine |
Volume | 34 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2013 |
Keywords
- ADP-ribosylation
- ARTD1
- Activity
- Chromatin
- Gene expression
- PARP-1
- Poly(ADP-ribose)
- Posttranslational modification
- Regulation
- Transcription
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry