Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Poly(ADP-ribose) polymerase-1 (
PARP-1
) is an important regulator of apoptosis. Its over-activation at the onset of apoptosis can inhibit the action of apoptotic endonucleases like caspase-activated DNase and DNAS1L3. Therefore, controlled
PARP-1
proteolysis during caspase-dependent apoptosis is considered essential to promote DNA degradation. Yet, little is known about the interplay of
PARP-1
and endonucleases that operate during caspase-independent cell death. Here we show that in the long-term cultured HeLa cells which undergo caspase-independent death,
PARP-1
co-immunoprecipitates with
leukocyte elastase
inhibitor-derived DNase II (L-DNase II), an acid DNase implicated in this death pathway and activated by serine proteases. Our results indicate that, despite having putative poly(ADP-ribose)-acceptor sites, LEI/L-DNase II is neither significantly poly(ADP-ribosyl)ated nor inhibited by
PARP-1
during caspase-independent apoptosis. Unexpectedly, caspase-independent apoptosis induced by hexa-methylene amiloride, LEI/L-DNase II can activate
PARP-1
and promote its auto-poly(ADP-ribosyl)ation, thus inhibiting
PARP-1
activity. Moreover, overexpression of LEI blocks the pro-survival effect of
PARP-1
in this model of cell death. Our results provide the original evidence for a new mechanism of
PARP-1
activity regulation in the caspase-independent death pathway involving LEI/L-DNase II.
...
PMID:Regulation of poly(ADP-ribose) polymerase-1 functions by leukocyte elastase inhibitor/LEI-derived DNase II during caspase-independent apoptosis. 1895 96
Poly(ADP-ribose) polymerase-1 (
PARP-1
) uses NAD(+) as a substrate to form ADP-ribose. During apoptosis, caspases cleave
PARP-1
to avoid excessive NAD consumption. Because
PARP-1
is a key regulator of the activity of DNases involved in caspase-dependent apoptosis, its cleavage is required to promote DNA degradation. To explore the situation in caspase-independent cell death, we investigated the effect of
PARP-1
on the acid endonuclease
leukocyte elastase
inhibitor (LEI)-derived DNase II (L-DNase II). We found for the first time an association between
PARP-1
and LEI/L-DNase II. Unexpectedly, we observed that LEI influenced the automodification of
PARP-1
.
...
PMID:Leukocyte elastase inhibitor: a new regulator of PARP-1. 1972 34
