FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration

Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule n...

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Main Authors: Fung, E, Richter, C, Yang, H, Schäffer, I, Fischer, R, Kessler, B, Bassermann, F, D'Angiolella, V
Format: Journal article
Language:English
Published: EMBO Press 2018
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author Fung, E
Richter, C
Yang, H
Schäffer, I
Fischer, R
Kessler, B
Bassermann, F
D'Angiolella, V
author_facet Fung, E
Richter, C
Yang, H
Schäffer, I
Fischer, R
Kessler, B
Bassermann, F
D'Angiolella, V
author_sort Fung, E
collection OXFORD
description Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192. Among these, CEP192 is specifically targeted for proteasomal degradation by FBXL13. Accordingly, induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high levels of CEP192 and γ-tubulin at the centrosomes with the consequence of defects in cell motility. Together, we characterise FBXL13 as a novel regulator of microtubule nucleation activity and highlight a role in promoting cell motility with potential tumour-promoting implications.
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spelling oxford-uuid:58a4b02d-d9d8-4d2a-9cf5-44f7d5e4d69f2022-03-26T17:04:52ZFBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migrationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:58a4b02d-d9d8-4d2a-9cf5-44f7d5e4d69fEnglishSymplectic Elements at OxfordEMBO Press2018Fung, ERichter, CYang, HSchäffer, IFischer, RKessler, BBassermann, FD'Angiolella, VAberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192. Among these, CEP192 is specifically targeted for proteasomal degradation by FBXL13. Accordingly, induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high levels of CEP192 and γ-tubulin at the centrosomes with the consequence of defects in cell motility. Together, we characterise FBXL13 as a novel regulator of microtubule nucleation activity and highlight a role in promoting cell motility with potential tumour-promoting implications.
spellingShingle Fung, E
Richter, C
Yang, H
Schäffer, I
Fischer, R
Kessler, B
Bassermann, F
D'Angiolella, V
FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration
title FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration
title_full FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration
title_fullStr FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration
title_full_unstemmed FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration
title_short FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration
title_sort fbxl13 directs the proteolysis of cep192 to regulate centrosome homeostasis and cell migration
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