What happens in ADP-ribosylation?
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. Improper ADP-ribosylation has been implicated in some forms of cancer.
What is the purpose of ADP-ribosylation?
ADP-ribosylation (ADPr) is a reversible post-translational modification of proteins, which controls major cellular and biological processes, including DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses.
What is PARP cleavage?
The poly(ADP-ribose) polymerase (PARP-1), a 113 kDa nuclear enzyme, is cleaved in fragments of 89 and 24 kDa during apoptosis. This cleavage has become a useful hallmark of apoptosis and has been shown to be done by DEVD-ase caspases, a family of proteases activated during apoptosis.
What is ADP-ribosylation catalyzed by diphtheria toxin?
Diphtheria toxin catalyzes the ADP ribosylation of the diphthamide residue of eukaryotic elongation factor 2 (eEF-2). Isotope trapping experiments yield a commitment to catalysis of 0.24 at saturating eEF-2 concentrations, resulting in suppression of the intrinsic isotope effects.
What is ADP-ribosylation of elongation factor 2?
Eukaryotic elongation factor 2 is the target of a class of bacterial mono-ADP-ribosyltransferase toxins which include the prototype, DT, exotoxin A from P. aeruginosa, and cholix toxin from V. cholera. Exposure of eukaryotic cells to these toxins leads to inhibition of protein synthesis and cell growth.
How is PARP activated?
PARP can be activated in cells experiencing stress and/or DNA damage. ATP depletion in a cell leads to lysis and cell death (necrosis). PARP also has the ability to induce programmed cell death, via the production of PAR, which stimulates mitochondria to release AIF. This mechanism appears to be caspase-independent.
What is the role of PARP in apoptosis?
During the execution phase of apoptosis, PARP-1 is specifically proteolyzed by caspases to produce an N-terminal DNA- binding domain (DBD) and a C-terminal catalytic fragment. The functional consequence of this proteolytic event is not known.
What is a PARP protein?
Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.
What is poly ADP ribosylation?
PolyADP-ribosylation, also known as parylation, is the post-translational modification process by which polymers of ADP-ribose (poly(adenosinediphosphate-ribose)) are covalently attached to proteins by PAR polymerase enzymes.