The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium
The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anapha...
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doaj-81ec39744a044a1695a9591637a4d5f92021-05-04T23:25:17ZengeLife Sciences Publications LtdeLife2050-084X2014-08-01310.7554/eLife.03083The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary ciliumWeiping Wang0Tao Wu1Marc W Kirschner2Department of Systems Biology, Harvard Medical School, Boston, United StatesDepartment of Systems Biology, Harvard Medical School, Boston, United StatesDepartment of Systems Biology, Harvard Medical School, Boston, United StatesThe primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly.https://elifesciences.org/articles/03083primary cilumubiquitincell cycleretinal cell culture |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weiping Wang Tao Wu Marc W Kirschner |
spellingShingle |
Weiping Wang Tao Wu Marc W Kirschner The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium eLife primary cilum ubiquitin cell cycle retinal cell culture |
author_facet |
Weiping Wang Tao Wu Marc W Kirschner |
author_sort |
Weiping Wang |
title |
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_short |
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_full |
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_fullStr |
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_full_unstemmed |
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_sort |
master cell cycle regulator apc-cdc20 regulates ciliary length and disassembly of the primary cilium |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2014-08-01 |
description |
The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly. |
topic |
primary cilum ubiquitin cell cycle retinal cell culture |
url |
https://elifesciences.org/articles/03083 |
work_keys_str_mv |
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_version_ |
1721476988448800768 |