PARP1 Antibodies

Poly [ADP-ribose] polymerase 1 (PARP1)

Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin structure and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway resulting in the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272).

With EEF1A1 and TXK, forms a complex that serves as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its own transcription, and is consequently involved importantly in Th1 cytokine production (PubMed:17177976). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272).

Gene Information

Human
Gene Name:	PARP1
Uniprot:	P09874
Entrez:	142

Family

Belongs to:
No superfamily

Alternative Names

ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase); ADPRT 1; ADPRT; ADPRTADP-ribosyltransferase NAD(+); EC 2.4.2; EC 2.4.2.30; NAD(+) ADP-ribosyltransferase 1; PARP apoptosis; PARP; PARP1; PARP-1; PARPADPRT1; poly (ADP-ribose) polymerase 1; poly (ADP-ribose) polymerase family, member 1; poly [ADP-ribose] polymerase 1; poly(ADP-ribose) polymerase; poly(ADP-ribose) synthetase; poly(ADP-ribosyl)transferase; Poly[ADP-ribose] synthase 1; PPOL; PPOLpADPRT-1

Molecular Weight

Mass (kDA):
113.084 kDA

Genomic Context

Human
Location:	1q42.12
Sequence:	1; NC_000001.11 (226360691..226408093, complement)

Subcellular Localizations

Nucleus. Nucleus, nucleolus. Chromosome. Localizes to sites of DNA damage.

Diseases

• Malignant Neoplasms
• Neoplasms
• Malignant Neoplasm Of Breast
• Mammary Neoplasms
• Carcinoma
• Inflammation
• Leukemia
• Carcinogenesis
• Malignant Paraganglionic Neoplasm
• Genomic Instability
• Adenocarcinoma
• Cell Transformation, Neoplastic

• Neoplasm Metastasis
• Malignant Neoplasm Of Ovary
• Ischemia
• Liver Carcinoma
• Ovarian Neoplasm
• Malignant Neoplasm Of Lung
• Melanoma

Interacting Proteins

• APLF
• APTX
• CASP3
• CEBPA
• DNMT1

• E2F1
• ERG
• IL24
• OARD1
• PIAS4

• RECQL
• SNAI1
• Snai1
• SUMO1
• TP53

• UBC
• WRN
• XRCC1
• YARS
• ZNF423

Pathways

• Cell Death
• Dna Repair
• Cell Cycle
• Cell Proliferation
• Induction Of Apoptosis
• Cell Growth
• Pathogenesis
• Aging
• Localization
• Cell Cycle Arrest
• Programmed Cell Death
• Dna Replication
• Methylation

• Autophagy
• Rna Interference
• Chromatin Remodeling
• Proteolysis
• Mitosis
• Inflammatory Response
• Senescence

PTMs

• Cleavage
• Phosphorylation
• Ribosylation
• Methylation
• Ubiquitination
• Acetylation
• Reduction
• Demethylation

• Sumoylation
• Dephosphorylation
• Nitration
• Deacetylation
• Nitrosylation
• Oxidation
• Biotinylation
• Amidation

• Palmitoylation

Research Areas

• Apoptosis
• Base Excision Repair
• Cancer
• Core ESC-Like Genes
• DNA Repair

• Hypoxia
• Stem Cell Markers
• Tumor Suppressors

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/PARP1

Best Uses Of The PARP1 Marker

This article explains the mechanisms behind the breakdown of PARP1 protein. PARP-1 is broken down by Granzyme. Cathepsin cleaves PARP-1. Granzyme action is a very vital component of PARP-1's cleavage. Here are a few examples of how Granzyme action is able to break down PARP1.

The Gra-B cleaves the PARP-1

During cell death, Gra-B cleaves PARP-1). This protein has perforin-dependent translocation and shares the same substrate specificity as caspase-3, although it is more efficient in the process of causing cell death. It also plays a role in the process of apoptosis without caspases and may even activate Bid. Find out more about this protein and its possible role in the death of cells.

The WGR domain is the most prominent feature of PARP-1. It plays an important role in DNA-dependent activation. The WGR domain binds with the DNA molecule in a similar manner to the PARP-1-8 mer complex. Similarly, the DNA-dependent poly(ADP-ribosylation)ation domains are arranged in a pyramidal shape.

This protein is responsible for fundamental functions under oxidative stress conditions. It's a double-edged ax in that it can cause damage to cells or restore it to its normal state. It is also cleaved by suicide proteases. In this instance the PARP-1 fragment gets linked to damaged DNA strands irreparably which reduces the rate of DNA repair and also preserves cell ATP pools.

Caspase-7 and -B cleave the PARP-1 protein in vivo. The catalytic portion of PARP-1 is an 89-kD area, while the area that is cleaved has zinc-finger-like motif. This enzyme is also able to regulate cell death through cutting off PARP-1. Caspases-mediated PARP-1 cleavage is complicated by the absence of NAD and activatedDNA, which inhibit caspase-3.

Gra-B can cleave PARP-1 into fragments that have 64-kD N terminal and Cterminal domains of 54-kD. The 64-kD fragment at the N-terminal is inactive. However the 54-kD (and 42-kD) C-terminal fragments can be catalytically active. This protein cleavage-induced conformational changes within the molecule were achieved by CORAL, using CORAL, to create structural models of PARP-1 compounds.

PARP-1 is a DNA-dependent ADP-ribosyltransferase. It is often associated with chromatin. PARP-1 is a protein that binds to damaged DNA and nuclear proteins, like HPF-1, and has been linked with the transcription of genes in cancer cells. PARP-1's activity can also alter the structure of nucleosomes as well as chromatin.

Gra-A cleaves PARP-1

Gra-A cleaves PARP-1/PARP-1 during the induction of cell death. It is a perforin dependent protein that shares a substrate-specificity similar to caspase-3. It also triggers more rapid cell death than the caspases. It can trigger apoptosis certain circumstances without the presence caspases. However, it is also capable of activating other caspases including Bid.

PARP-1's function is not completely understood. The protein is involved in cell death proteases such as the caspases, calpains and cathepsins and the granzymes. These proteases cleave PARP-1 , and create fragments that have a certain molecular weight. These fragments regulate different forms of cell death. The enzyme Gra-A cleaves PARP-1.

The function of PARP-1 is multifaceted and complex. It regulates energy levels in cells, inflammatory mediators, as well as death pathways. It also plays a part in the regulation of gene transcription, sexhormone signals and mitosis. PARP-1 can be anti-tumor or pro-tumor, depending on the situation. Therefore, PARP inhibitors must be used with caution. For example, Gra-A cleaves PARP-1 in prostate cancer.

A fragment of around 50 kD is produced when caspases break down PARP-1. This fragment is the one that is most active in necrotic cell death. Its pattern of fragmentation is similar to cathepsin G however, it produces less intensity and requires a longer period of incubation. A single protein that cleaves PARP-1 could also cleave other proteins.

PARP-1 activity is controlled by numerous other factors including the methylation process. Methylation patterns can be described as functional equivalents to gene mutations. PARP-1 inhibition is associated transcriptional silencing and DNA methylation, and hypermethylation CpG islands. Additionally, PARP-1 inhibition hinders CTCF, a chromatin insulator that binds hypomethylated DNA regions.

DNA damage can promote the formation of a complex that includes PARP-1. The structure of the PAR chain is utilized to trigger the NF-kb receptor. In addition to controlling the destruction of cells, PARP-1 also plays a role in biochemical signaling. PARP-1 also regulates microglial and the function of astrocytes. It is thought that reduced PARP-1 activity can cause programmed death of neurons and memory consolidation.

Granzyme action is what forms PARP-1 fragments

Researchers have found that the enzyme granzymeB is involved in activating the cell death pathway ICE dependent in certain cell types. Granzyme B requires an Ac-DEVD inhibitable CHO protease downstream of its CPP32-like counterpart. The enzyme is activated and disintegrates PARP-1, which is crucial for the process of apoptosis.

The PARP-1 cleavage products comprise necrotic and apoptotic fragments. The size can vary from 50 to 80 kDa and the pattern is consistent with the cleavage process by cathepsin. These fragments are too big for qRTPCR to identify. PARP-1 fragments can be identified by cleavage of DNA using granzyme.

PARP-1 regulates cellular energy and death pathways. It also affects gene transcription, sexhormone signals, ERK signaling and mitosis. Its actions are dependent on the environment in which it is activated. PARP inhibitors can alter the actions of other proteins. It is therefore essential to consider PARP-1's role in the development of tumors and their progression.

Scientists investigated whether EBOV causes cell death in macrophages derived from human monocytes. They found that EBOV infection resulted in a weak sign of apoptotic PARP-1 but significantly higher levels of necrotic PARP-1. In addition, increased PAR levels led to autophagy and necrosis. These findings suggest that granzyme inhibitors can stimulate the process of apoptosis.

Granzyme B is a monomer which has 27-29kDa. It is similar to protease and chymotrypsin. Granzyme B is cleaved only after aspartic acid residues. Its particularity is similar to caspases which are cysteine proteases that stimulate apoptosis. Moreover, granzyme B activates the protein known as SET, which relieves the inhibition of NME-1, an enzyme that is responsible for DNA synthesizing.

Additionally, PARP-1 serves roles that go beyond repair of DNA. Its functions include triggering or preventing the six characteristics of cancer. By regulating the expression level of PARP-1, these inhibitors can affect cancer growth. Its inhibition could also increase the sensitivity of cytotoxic drugs. PARP-1 inhibitors are a promising treatment option for tumors that resist a MEK inhibitor.

Cathepsin cleaves PARP-1

When necrotic cells die, PARP-1 is broken into 50-kD fragments through lymphosomes and lysosomal proteases. H 2 O 2 10% alcohol and HgCl2 trigger necrosis. Cathepsin B and -D are proteins that break down PARP-1. These proteases release active PARP-1 fragments that are 55-kD and 42-kD respectively when necrotic cells die.

Although cathepsin has a myriad of targets but the cleavage of PARP-1 by BRCT as well as granzymes appears to be the most important. The Zn1 and Zn2 domains were previously identified as RNA-binding protein in PARP-1. These domains were then tested for their effect on PARP-1 proteolysis, using the cleavage test using RNase. The results revealed that both BRCT and Zn3 domains are able to cleave PARP-1 at the exact rate, regardless of their interaction with RNase.

Cathepsins play an important role in cell death, as they cause lysosomal fracture. ROS production is increased due to PARP-1 being cleaved with Gra-A. This effect is countered by an increase in poly (ADPribosyl),ation of PARP-1. The Gra-A and -B proteins are also involved in necrosis and parthanatosis. Cathepsin reduces PARP-1 in the residues Lysine 498 and Leucine 525. Both fragments produce multiple fragments.

PARP-1 plays a variety of physiological and pathological functions. However, it was initially identified as a DNA binding enzyme that starts repair of base excision. It also plays a role in repair of nucleotide excisions, single-strand repair of bases mediated by DNA ligase III poly (ADP-ribose) and flap endonuclease-1 and XRCC1. Additionally, it is involved in double-strand repair through an alternative, non-homologous ending joining pathway.

It is not entirely certain what PARP-1 does in angiogenesis. While PARP-1 is involved in the growth and maintenance of blood vessels, it isn't exactly clear what its function is. Recent studies suggest that PARP-1 could play a role in angiogenesis in a variety ways. Further research is needed to determine whether PARP-1 plays part in the process of tumor angiogenesis.

While this mechanism isn't completely comprehended, it is believed to be applicable to other RNA-binding proteins. This study identified a motif that is recognized by the caspase-7 excosite. It also revealed how the exosite breaks down PARP-1 and other RNA-BPs. Positive charges also play an essential role in the cleavage PARP-1.