Poly (ADP-ribose) polymerase 1(PRAP1), also known as NAD(+) ADP-ribosyltransferase 1(ADPRT), is a chromatin-associated enzyme which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The ADP-D-ribosyl group of NAD+ is transferred to an acceptor carboxyl group on a histone or the enzyme itself, and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. The poly(ADP-ribosyl)ation modification is critical for a wide range of processes, including DNA repair, regulation of chromosome structure, transcriptional regulation, mitosis and apoptosis. PARP1 is demonstrateed to mediate the poly(ADP-ribose) ation of APLF (aprataxin PNK-like factor) and CHFR (checkpoint protein with FHA and RING domains), two representative proteins involved in the DNA damage response and checkpoint regulation. Further, It has been suggested that DNA-dependent protein kinase (DNA-PK), another component of DNA repair, suppresses PARP activity, probably through direct binding and/or sequestration of DNA-ends which serve as an important stimulator for both enzymes. PARP1 inhibitors is thus proposed as a targeted cancer therapy for recombination deficient cancers, such as BRCA2 tumors.
Regenerating islet-derived protein 4, also known as REG-like protein, REG4, GISP and RELP, a member of the regenerating gene family belonging to the calcium (C-type) dependent lectin superfamily, has been found to be involved in malignancy in several different organs including the stomach, colorectum, pancreas and prostate. It is highly expressed in the gastrointestinal tract and markedly up-regulated in colon adenocarcinoma, pancreatic cancer, gastric adenocarcinoma, and inflammatory bowel disease. Expression of the Reg4 in different cell types has been associated with regeneration, cell growth and cell survival, cell adhesion and resistance to apoptosis. REG4 protein overexpression is associated with an unfavorable response to preoperative chemoradiotherapy and may be used as a predictive biomarker clinically. REG4 may play an important role in the development and progression of colorectal cancer, as well as in intestinal morphogenesis and epithelium restitution.
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.
Parvalbumin α (PVALB) is a member of the parvalbumin family. PVALB is a high affinity calcium ion-binding protein, with two EF hand domains. PVALB is structurally and functionally similar to calmodulin and troponin C, it can bind two calcium ions. Parvalbumin is thought to be involved in relaxation after contraction in muscle. Parvalbumin is expressed in a specific population of GABAergic interneurons, which are believed to have a role in maintaining the balance between excitation and inhibition in the cortex as well as the hippocampus.
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4(PIN4) is a peptidyl-prolyl cis/trans isomerase (PPIase) which interacts with NIMA and is vital for cell cycle regulation. PIN4 has 2 different isoforms: PAR14 and PAR17. Furthermore, PIN4 protein binds to double-stranded DNA under physiological salt conditions. PIN4 is involved as a ribosomal RNA processing factor in ribosome biogenesis. The PAR14 binds to tightly bent AT-rich stretches of double-stranded DNA, but PAR17 binds to double-stranded DNA.
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