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: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To study the pathways associated with genomic instability in cancer, we examined UV-induced and spontaneous mutagenesis in clonal cell lines expressing human papillomavirus (HPV) proteins, either high-risk (HPV16) E6 or E7 or low-risk (HPV11) E6, in comparison to the parental RKO cells, a colon carcinoma cell line expressing only normal
p53
. High-risk E6 and E7 bind and functionally inactivate tumor suppressor proteins
p53
and Rb, respectively, and both disrupt the G1 arrest in response to DNA damage. Low-risk HPV E6 proteins bind
p53
with much lower affinity than high-risk E6 and fail to mediate
p53
degradation or to disrupt the G1 checkpoint. We found that cells expressing HPV16 E6 had reduced survival and increased mutagenesis at the hprt locus when treated with low doses of UV. However, this analysis was complicated by the unexpected observation of a very high background of spontaneous mutagenesis in the unirradiated cells expressing the HPV16 E6 gene.
Fluctuation
analysis revealed a 5-fold elevated mutation rate in the cells expressing HPV16 E6. HPV11 E6 conferred a 2-fold elevation in the mutation rate, but HPV16 E7 had no effect. The increased spontaneous mutagenesis, therefore, appeared to be mediated by
p53
inactivation and to be independent of Rb (which acts downstream of
p53
in the G1 arrest pathway following DNA damage). Taken together, these findings suggest that the effect of
p53
inactivation on spontaneous mutagenesis is manifested at the level of DNA repair, recombination, or coupling of transcription with one of these processes instead of by an alteration in G1 arrest.
...
PMID:p53 inactivation by HPV16 E6 results in increased mutagenesis in human cells. 767 Dec 55
The aim of our present study was to elucidate the effects of up-regulation and down-regulation of intracellular reactive oxygen species (ROS) level on proliferation, migration, and related molecular mechanism. Breast cancer cells were treated by catalase or H
2
O
2
. MTT, colony formation assay, and Hoechst/PI staining were used to evaluate proliferation and apoptosis. The level of intracellular ROS was measured by dichlorodihydrofluorescein diacetate probes. The ability of migration was detected by wound healing. Western blotting and coimmunoprecipitation (co-IP) were used to determine the expression of DLC1 and CAV-1 and their interaction. Our data indicated that up-regulation of intracellular ROS induced by H
2
O
2
significantly inhibited proliferation and induced apoptosis accompanying G1 cell cycle arrest and elevated expression of
p53
. For cell migration, either up-regulation or down-regulation of ROS induced migration inhibition with reduction of interaction between DLC1 and CAV-1. Our results suggested that up-regulation of intracellular ROS inhibited proliferation by promoting expression of
p53
and induced G1 cycle arrest and apoptosis.
Fluctuation
of ROS inhibited migration through reducing the interaction between DLC1 and CAV-1.
...
PMID:Fluctuation of ROS regulates proliferation and mediates inhibition of migration by reducing the interaction between DLC1 and CAV-1 in breast cancer cells. 2813 Jul 53
