| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-123 |
Sentence |
denotes |
Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. |
| T2 |
124-298 |
Sentence |
denotes |
The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone deacetylase that plays a critical role in transcriptional silencing, genome stability, and longevity. |
| T3 |
299-407 |
Sentence |
denotes |
A human homologue of Sir2, SIRT1, regulates the activity of the p53 tumor suppressor and inhibits apoptosis. |
| T4 |
408-566 |
Sentence |
denotes |
The Sir2 deacetylation reaction generates two products: O-acetyl-ADP-ribose and nicotinamide, a precursor of nicotinic acid and a form of niacin/vitamin B(3). |
| T5 |
567-723 |
Sentence |
denotes |
We show here that nicotinamide strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of a sir2 mutant. |
| T6 |
724-909 |
Sentence |
denotes |
Nicotinamide abolishes silencing and leads to an eventual delocalization of Sir2 even in G(1)-arrested cells, demonstrating that silent heterochromatin requires continual Sir2 activity. |
| T7 |
910-1022 |
Sentence |
denotes |
We show that physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. |
| T8 |
1023-1184 |
Sentence |
denotes |
The degree of inhibition by nicotinamide (IC(50) < 50 microm) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. |
| T9 |
1185-1336 |
Sentence |
denotes |
We propose a model whereby nicotinamide inhibits deacetylation by binding to a conserved pocket adjacent to NAD(+), thereby blocking NAD(+) hydrolysis. |
| T10 |
1337-1438 |
Sentence |
denotes |
We discuss the possibility that nicotinamide is a physiologically relevant regulator of Sir2 enzymes. |
