CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere.

Niikura, Yohei; Kitagawa, Risa; Ogi, Hiroo; Abdulle, Rashid; Pagala, Vishwajeeth; Kitagawa, Katsumi

CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere.

Niikura, Yohei; Kitagawa, Risa; Ogi, Hiroo; Abdulle, Rashid; Pagala, Vishwajeeth; Kitagawa, Katsumi.

Afiliación

Niikura Y; Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Kitagawa R; Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Ogi H; Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Abdulle R; Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Pagala V; Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Kitagawa K; Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatrics, College of Medicine, The Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA. Electronic address: katsum

Dev Cell ; 32(5): 589-603, 2015 Mar 09.

Article en En | MEDLINE | ID: mdl-25727006

RESUMEN

CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) and CENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that "signaling" ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.

Asunto(s)

Autoantígenos/metabolismo; Proteínas Portadoras/metabolismo; Centrómero/metabolismo; Proteínas Cromosómicas no Histona/metabolismo; Proteínas Cullin/metabolismo; Proteínas/metabolismo; Ubiquitina/metabolismo; Secuencia de Aminoácidos; Autoantígenos/genética; Western Blotting; Complejo del Señalosoma COP9; Proteínas Portadoras/genética; Células Cultivadas; Proteína A Centromérica; Proteínas Cromosómicas no Histona/genética; Segregación Cromosómica; Proteínas Cullin/genética; Técnica del Anticuerpo Fluorescente; Células HeLa; Histonas/metabolismo; Humanos; Técnicas para Inmunoenzimas; Luciferasas/metabolismo; Lisina/química; Lisina/genética; Lisina/metabolismo; Datos de Secuencia Molecular; Nucleosomas/metabolismo; Unión Proteica; Proteínas/genética; ARN Mensajero/genética; Reacción en Cadena en Tiempo Real de la Polimerasa; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Homología de Secuencia de Aminoácido; Ubiquitinación

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoantígenos / Proteínas Cromosómicas no Histona / Proteínas / Proteínas Portadoras / Centrómero / Ubiquitina / Proteínas Cullin Límite: Humans Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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