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)
Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that
PER
2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of
PER
2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when
PER
2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of
PER
2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of
PER
2 alone or in combination with CRY 2. Expression of
PER
2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in
PARP
[poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that
PER
2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels.
...
PMID:Period-2: a tumor suppressor gene in breast cancer. 1833 30
Circadian clocks in peripheral organs are tightly coupled to cellular metabolism and are readily entrained by feeding-fasting cycles. However, the molecular mechanisms involved are largely unknown. Here we show that in liver the activity of
PARP-1
, an NAD(+)-dependent
ADP-ribosyltransferase
, oscillates in a daily manner and is regulated by feeding. We provide biochemical evidence that
PARP-1
binds and poly(ADP-ribosyl)ates CLOCK at the beginning of the light phase. The loss of
PARP-1
enhances the binding of CLOCK-BMAL1 to DNA and leads to a phase-shift of the interaction of CLOCK-BMAL1 with
PER
and CRY repressor proteins. As a consequence, CLOCK-BMAL1-dependent gene expression is altered in
PARP-1
-deficient mice, in particular in response to changes in feeding times. Our results show that Parp-1 knockout mice exhibit impaired food entrainment of peripheral circadian clocks and support a role for
PARP-1
in connecting feeding with the mammalian timing system.
...
PMID:Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. 2094 68
