CENP-A Ubiquitylation Is Indispensable to Cell Viability.

Cell Survival Centromere Protein A / metabolism Female Humans Mutant Proteins / metabolism Peptides / metabolism Protein Binding Ubiquitination
CENP-A centromere centromere identity conditional knockout system epigenetics kinetochore mitosis monoubiquitin posttranslational modifications (PTMs) ubiquitylation

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
23 09 2019
Historique:
received: 24 09 2018
revised: 30 04 2019
accepted: 14 07 2019
entrez: 25 9 2019
pubmed: 25 9 2019
medline: 19 5 2020
Statut: ppublish

Résumé

CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects in centromere localization and cell viability. In the present study, we found that EYFP tagging induces additional ubiquitylation of EYFP-CENP-A K124R, which allows the mutant protein to bind to HJURP. Using a previously developed conditional CENP-A knockout system and our CENP-A K124R knockin mutant created by the CRISPR-Cas9 system, we show that the Flag-tagged or untagged CENP-A K124R mutant is lethal. This lethality is rescued by monoubiquitin fusion, indicating that CENP-A ubiquitylation is essential for viability.

Identifiants

DOI: 10.1016/j.devcel.2019.07.015 PMID: 31550462 PMC: PMC6761987
pubmed: 31550462
pii: S1534-5807(19)30621-5
doi: 10.1016/j.devcel.2019.07.015
pmc: PMC6761987
mid: NIHMS1535109
pii:
doi:

Substances chimiques

Centromere Protein A 0
Mutant Proteins 0
Peptides 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

683-689.e6

Subventions

Organisme : NCI NIH HHS
ID : R21 CA205659
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Références

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Auteurs

Yohei Niikura (Y)

Greehey Children's Cancer Research Institute, Department of Molecular Medicine, UT Health Science Center San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229-3000, USA; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu Province 210061, China. Electronic address: niikura@nicemice.cn.

Risa Kitagawa (R)

Greehey Children's Cancer Research Institute, Department of Molecular Medicine, UT Health Science Center San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229-3000, USA.

Lei Fang (L)

Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province 210093, China.

Katsumi Kitagawa (K)

Greehey Children's Cancer Research Institute, Department of Molecular Medicine, UT Health Science Center San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229-3000, USA. Electronic address: kitagawak@uthscsa.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › CENP-A Ubiquitylation Is Indispensable to Cell...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Autoantigènes › Protéine A du centromère › CENP-A Ubiquitylation Is Indispensable to Cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CENP-A Ubiquitylation Is Indispensable to Cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mutantes › CENP-A Ubiquitylation Is Indispensable to Cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › CENP-A Ubiquitylation Is Indispensable to Cell...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › CENP-A Ubiquitylation Is Indispensable to Cell...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Ubiquitination › CENP-A Ubiquitylation Is Indispensable to Cell...