Proteomics

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FBXL13 regulates centrosome homeostasis and migration through ubiquitin- mediated proteolysis

ABSTRACT: Aberrant centrosome organization with ensuing alterations of microtubule nucleation enables tumor cells to proliferate and invade despite increased genomic instability. CEP192 is a key factors 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 degredation 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 corresponding to defects in cell motility. Together, we characterize FBXL13 as a novel regulator of microtubule nucleation activity and highlight a role in promoting cell motility with potential tumor-promoting implications.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Kidney

SUBMITTER: Roman Fischer  

LAB HEAD: Roman Fischer

PROVIDER: PXD008310 | Pride | 2018-01-16

REPOSITORIES: Pride

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OTE0042_Vincenzo_L13iso1+MLN.pride.mgf.gz Mgf
OTE0042_Vincenzo_L13iso1.mgf Mgf
OTE0042_Vincenzo_L13iso1.pride.mgf.gz Mgf
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Publications

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

Fung Ella E   Richter Carmen C   Yang Hong-Bin HB   Schäffer Isabell I   Fischer Roman R   Kessler Benedikt M BM   Bassermann Florian F   D'Angiolella Vincenzo V  

EMBO reports 20180118 3

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 centrosome  ...[more]

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