| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-90 |
Sentence |
denotes |
Increased protein stability causes DNA methyltransferase 1 dysregulation in breast cancer. |
| T2 |
91-182 |
Sentence |
denotes |
We report that DNA methyltransferase 1 (DNMT1) expression is dysregulated in breast cancer. |
| T3 |
183-298 |
Sentence |
denotes |
The elevated protein levels are not a result of increased mRNA levels, but rather an increase in protein half-life. |
| T4 |
299-535 |
Sentence |
denotes |
We found that DNMT1 protein levels were elevated in breast cancer tissues and in MCF-7 breast cancer cells relative to normal human mammary epithelial cells (HMECs) without a concomitant increase in DNMT1 mRNA or proliferative fraction. |
| T5 |
536-683 |
Sentence |
denotes |
Although DNMT1 mRNA levels were properly S-phase-regulated in both cell types, DNMT1 protein levels did not follow S-phase fraction in MCF-7 cells. |
| T6 |
684-930 |
Sentence |
denotes |
Rather, an increase in DNMT1 protein stability was found for MCF-7 cells relative to HMECs, and a destruction domain was mapped to the N-terminal 120 amino acids of DNMT1, which was required for its proper ubiquitination and degradation in HMECs. |
| T7 |
931-1136 |
Sentence |
denotes |
Furthermore, overexpression of DNMT1 with this deleted destruction domain in HMECs resulted in significantly increased genomic 5-methylcytosine levels relative to overexpression of the full-length protein. |
| T8 |
1137-1288 |
Sentence |
denotes |
The regulation of DNMT1 destruction via this domain may be dysfunctional in cancer cells leading to subsequent cytosine hypermethylation in the genome. |
