東北大学加齢医学研究所 加齢医学研究拠点 | Institute of Development, Aging and Cancer, Tohoku University

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◇平成25年12月9日(月)加齢研セミナ-のご案内
日時: 平成25年12月9日(月)16時30分~
場所: 加齢研SA棟 国際会議室
演題: CENP-A K124 Ubiquitylation Is an Epigenetic Mark for Centromere Identity
講師: 北川 克己
所属: Center for Childhood Cancer
The Research Institute at Nationwide Children’s Hospital Department of Pediatrics The Ohio State University College of Medicine
担当: 田中耕三 (所属 分子腫瘍学研究分野 ・内線 8491 )
要旨: CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity thereby ensuring kinetochore assembly and proper chromosome segregation. The precise mechanism by which its specific localization within centromeric heterochromatin remains obscure. We have discovered that the CUL4A-RBX1-COPS8 E3 ligase activity, mediated by the SGT1-HSP90 complex, is required for CENP-A ubiquitylation on lysine 124 (K124) and centromere localization. A CENP-A K124R mutation abrogates centromere localization, and addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres, indicating that K124 “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. We show that pre-existing ubiquitylated CENP-A is necessary for the recruitment of newly synthesized CENP-A to the centromere indicating that CENP-A K124 ubiquitylation is an epigenetic mark. We found that overexpression of mono-ubiquitin fused CENP-A induced formation of putative neocentromeres in human cells. These results provide compelling evidence that K124 ubiquitylation is an epigenetic mark for centromere identity.

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