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)
Hyperplasia
of synovial lining cells is one of the main features of rheumatoid arthritis (RA). We previously reported that ERBB2 is highly expressed in RA synovial cells and that it plays an important role in their hyperproliferative growth. Recent findings have suggested that poly(ADP-ribose) polymerase-1 (
PARP-1
) is involved in the transactivation of NF-kappaB-dependent genes such as ERBB2. In the present study, we investigated the role of
PARP-1
in ERBB2 transcription in RA synovial cells. The expression level of
PARP-1
was significantly high in synovial cells derived from three patients with RA, compared with three patients with osteoarthritis (OA). Luciferase assays revealed that
PARP-1
augments the transcription of the ERBB2 gene and that a region between -404 and -368 is responsible for this activation. A protein with an apparent molecular mass of 115 kDa was isolated mainly from nuclear extracts of RA synovial cells with an affinity matrix harboring a DNA fragment identical to the above region. Mass spectrometric analysis demonstrated this protein to be
PARP-1
. Southwestern blot analysis showed that
PARP-1
binds to this region, but not to adjacent regions.
PARP-1
associates directly with NF-kappaB, and a chromatin immunoprecipitation assay indicated that these proteins interact with this enhancer region in the ERBB2 gene. Treatment of RA synovial cells with
PARP-1
small interfering RNA attenuated their ERBB2 expression, while an inhibitor of the polymerase activity of
PARP-1
had no effect.
PARP-1
DNA binding is not required for transcriptional activation. These findings suggest that
PARP-1
is involved in the expression of ERBB2 in concert with NF-kappaB, which might be associated with the proliferation of RA synovial cells.
...
PMID:Involvement of poly(ADP-ribose) polymerase 1 in ERBB2 expression in rheumatoid synovial cells. 1574 88
Hyperplasia
suppressor gene (HSG), also called human mitofusin 2, is a novel gene that markedly suppresses the cell proliferation of hyperproliferative vascular smooth muscle cells from spontaneously hypertensive rat arteries. This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. In this report, we showed that an adenovirus vector encoding human HSG (Ad5-hHSG) had an antitumor activity in a wide range of cancer cell lines. We further focused on the lung cancer cell line A549 and the colon cancer cell line HT-29 and then observed that Ad5-hHSG induced apoptosis both in vitro and in vivo. Confocal laser scanning microscopy and electron microscopy revealed that cells infected with Ad5-hHSG formed dose-dependent perinuclear clusters of fused mitochondria. Adenovirus-mediated hHSG overexpression induced apoptosis, cell cycle arrest, mitochondrial membrane potential (DeltaPsim) reduction and release of cytochrome c, caspase-3 activation, and cleavage of
PARP
in vitro. Overexpression of hHSG also significantly suppressed the growth of subcutaneous tumors in nude mice both ex vivo and in vivo. In addition, Ad5-hHSG increased the sensitivity of these cell lines to two chemotherapeutic agents, VP16 and CHX, and radiation. These results suggest that Ad5-hHSG may serve as an effective therapeutic drug against tumors.
...
PMID:Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells. 1820 24
