期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 41, 页码 16564-16569出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1202639109
关键词
intra-molecular interaction; acetylation reporter; syntelin; TIP150; attachment error
资金
- Chinese 973 Project [2010CB912103, 2012CB111000, 2011CB966302, 2002CB713700]
- Chinese Academy of Science Grant [KSCX2-YW-H-10]
- Anhui Province Key Project Grant [08040102005]
- International Collaboration Grant [2009DFA31010]
- Chinese Natural Science Foundation [90508002, 91129714, 30830031]
- Fundamental Research Funds for Central Universities [WK2060190018]
- National Institutes of Health [DK56292, CA148133, G12RR03034, CA132389]
In eukaryotes, microtubules are essential for cellular plasticity and dynamics. Here we show that P300/CBP-associated factor (PCAF), a kinetochore-associated acetyltransferase, acts as a negative modulator of microtubule stability through acetylation of EB1, a protein that controls the plus ends of microtubules. PCAF acetylates EB1 on K220 and disrupts the stability of a hydrophobic cavity on the dimerized EB1 C terminus, which was previously reported to interact with plus-end tracking proteins (TIPs) containing the SxIP motif. As determined with an EB1 acetyl-K220-specific antibody, K220 acetylation is dramatically increased in mitosis and localized to the spindle microtubule plus ends. Surprisingly, persistent acetylation of EB1 delays metaphase alignment, resulting in impaired checkpoint silencing. Consequently, suppression of Mad2 overrides mitotic arrest induced by persistent EB1 acetylation. Thus, our findings identify dynamic acetylation of EB1 as a molecular mechanism to orchestrate accurate kinetochore-microtubule interactions in mitosis. These results establish a previously uncharacterized regulatory mechanism governing localization of microtubule plus-end tracking proteins and thereby the plasticity and dynamics of cells.
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