Abstract
The centromere plays an essential role in accurate chromosome segregation, and defects in its function lead to aneuploidy and thus cancer. The centromere-specific histone H3 variant CENP-A is proposed to be the epigenetic mark of the centromere, as active centromeres require CENP-A–containing nucleosomes to direct the recruitment of multiple kinetochore proteins. CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. However, the mechanism that controls the E3 ligase activity of the CUL4A-RBX1-COPS8 complex remains obscure. We have discovered that the SGT1-HSP90 complex is required for recognition of CENP-A by COPS8. Thus, the SGT1-HSP90 complex contributes to the E3 ligase activity of the CUL4A complex that is necessary for CENP-A ubiquitylation and CENP-A deposition at the centromere.
Original language | English (US) |
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Pages (from-to) | 1683-1694 |
Number of pages | 12 |
Journal | Cell Cycle |
Volume | 16 |
Issue number | 18 |
DOIs | |
State | Published - Sep 17 2017 |
Keywords
- CENP-A
- CUL4 E3 ligase
- HSP90
- SGT1
- SUGT1
- cancer
- cell cycle
- centromere
- epigenetic mark
- kinetochore
- mitosis
- ubiquitylation
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology