| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-164 |
Sentence |
denotes |
N terminus is essential for tropomyosin functions: N-terminal modification disrupts stress fiber organization and abolishes anti-oncogenic effects of tropomyosin-1. |
| T2 |
165-381 |
Sentence |
denotes |
Down-regulation of several key actin-binding proteins, such as alpha-actinin, vinculin, gelsolin, and tropomyosins (TMs), is considered to contribute to the disorganized cytoskeleton present in many neoplastic cells. |
| T3 |
382-473 |
Sentence |
denotes |
TMs stabilize actin filaments against the gel severing actions of proteins such as cofilin. |
| T4 |
474-632 |
Sentence |
denotes |
Among multiple TMs expressed in non-muscle cells, tropomyosin-1 (TM1) isoform induces stress fibers and functions as a suppressor of malignant transformation. |
| T5 |
633-751 |
Sentence |
denotes |
However, the molecular mechanisms of TM1-mediated cytoskeletal effects and tumor suppression remain poorly understood. |
| T6 |
752-858 |
Sentence |
denotes |
We have hypothesized that the ability of TM1 to stabilize microfilaments is crucial for tumor suppression. |
| T7 |
859-1040 |
Sentence |
denotes |
In this study, by employing a variant TM1, which contains an N-terminal hemagglutinin epitope tag, we demonstrate that the N terminus is a key determinant of tropomyosin-1 function. |
| T8 |
1041-1181 |
Sentence |
denotes |
Unlike the wild type TM1, the modified protein fails to restore stress fibers and inhibit anchorage-independent growth in transformed cells. |
| T9 |
1182-1376 |
Sentence |
denotes |
Furthermore, the N-terminal modification of TM1 disorganizes the cytoskeleton and delays cytokinesis in normal cells, abolishes binding to F-actin, and disrupts the dimeric associations in vivo. |
| T10 |
1377-1578 |
Sentence |
denotes |
The functionally defective TM1 allows the association of cofilin to stress fibers and disorganizes the microfilaments, whereas wild type TM1 appears to restrict the binding of cofilin to stress fibers. |
| T11 |
1579-1701 |
Sentence |
denotes |
TM1-induced cytoskeletal reorganization appears to be mediated through preventing cofilin interaction with microfilaments. |
| T12 |
1702-1873 |
Sentence |
denotes |
Our studies provide in vivo functional evidence that the N terminus is a critical determinant of TM1 functions, which in turn determines the organization of stress fibers. |