| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-116 |
Sentence |
denotes |
Triptolide-induced cell death in pancreatic cancer is mediated by O-GlcNAc modification of transcription factor Sp1. |
| T2 |
117-285 |
Sentence |
denotes |
Pancreatic cancer, the fourth most prevalent cancer-related cause of death in the United States, is a disease with a dismal survival rate of 5% 5 years after diagnosis. |
| T3 |
286-386 |
Sentence |
denotes |
One of the survival proteins responsible for its extraordinary ability to evade cell death is HSP70. |
| T4 |
387-571 |
Sentence |
denotes |
A naturally derived compound, triptolide, and its water-soluble prodrug, Minnelide, down-regulate the expression of this protein in pancreatic cancer cells, thereby causing cell death. |
| T5 |
572-643 |
Sentence |
denotes |
However, the mechanism of action of triptolide has not been elucidated. |
| T6 |
644-799 |
Sentence |
denotes |
Our study shows that triptolide-induced down-regulation of HSP70 expression is associated with a decrease in glycosylation of the transcription factor Sp1. |
| T7 |
800-956 |
Sentence |
denotes |
We further show that triptolide inhibits glycosylation of Sp1, inhibiting the hexosamine biosynthesis pathway, particularly the enzyme O-GlcNAc transferase. |
| T8 |
957-1066 |
Sentence |
denotes |
Inhibition of O-GlcNAc transferase prevents nuclear localization of Sp1 and affects its DNA binding activity. |
| T9 |
1067-1197 |
Sentence |
denotes |
This in turn down-regulates prosurvival pathways like NF-κB, leading to inhibition of HSF1 and HSP70 and eventually to cell death. |
| T10 |
1198-1380 |
Sentence |
denotes |
In this study, we evaluated the mechanism by which triptolide affects glycosylation of Sp1, which in turn affects downstream pathways controlling survival of pancreatic cancer cells. |
