Unknown

Dataset Information

0

APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment.


ABSTRACT: Recently, we have shown that a cancer causing truncation in adenomatous polyposis coli (APC) (APC(1-1450)) dominantly interferes with mitotic spindle function, suggesting APC regulates microtubule dynamics during mitosis. Here, we examine the possibility that APC mutants interfere with the function of EB1, a plus-end microtubule-binding protein that interacts with APC and is required for normal microtubule dynamics. We show that siRNA-mediated inhibition of APC, EB1, or APC and EB1 together give rise to similar defects in mitotic spindles and chromosome alignment without arresting cells in mitosis; in contrast inhibition of CLIP170 or LIS1 cause distinct spindle defects and mitotic arrest. We show that APC(1-1450) acts as a dominant negative by forming a hetero-oligomer with the full-length APC and preventing it from interacting with EB1, which is consistent with a functional relationship between APC and EB1. Live-imaging of mitotic cells expressing EB1-GFP demonstrates that APC(1-1450) compromises the dynamics of EB1-comets, increasing the frequency of EB1-GFP pausing. Together these data provide novel insight into how APC may regulate mitotic spindle function and how errors in chromosome segregation are tolerated in tumor cells.

SUBMITTER: Green RA 

PROVIDER: S-EPMC1237068 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment.

Green Rebecca A RA   Wollman Roy R   Kaplan Kenneth B KB  

Molecular biology of the cell 20050719 10


Recently, we have shown that a cancer causing truncation in adenomatous polyposis coli (APC) (APC(1-1450)) dominantly interferes with mitotic spindle function, suggesting APC regulates microtubule dynamics during mitosis. Here, we examine the possibility that APC mutants interfere with the function of EB1, a plus-end microtubule-binding protein that interacts with APC and is required for normal microtubule dynamics. We show that siRNA-mediated inhibition of APC, EB1, or APC and EB1 together give  ...[more]

Similar Datasets

| S-EPMC6205471 | biostudies-literature
| S-EPMC3244432 | biostudies-literature
| S-EPMC3432768 | biostudies-literature
| S-EPMC10499817 | biostudies-literature
| S-EPMC4678015 | biostudies-literature
| S-EPMC3998792 | biostudies-literature
| S-EPMC9934748 | biostudies-literature
| S-EPMC7657133 | biostudies-literature
| S-EPMC2196006 | biostudies-literature
2023-08-15 | PXD043164 | Pride