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.intra-molecular interaction | acetylation reporter | syntelin | TIP150 | attachment error

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The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. High-throughput sequencing data have laid a solid foundation for identifying genes related to cancer prognosis, but a gene marker is needed to predict clinical outcomes in HNSCC. In our study, we downloaded RNA Seq, single nucleotide polymorphism, copy number variation, and clinical follow-up data from TCGA. The samples were randomly divided into training and test. In the training set, we screened genes and used random forests for feature selection. Gene-related prognostic models were established and validated in a test set and GEO verification set. Six genes (PEX11A, NLRP2, SERPINE1, UPK, CTTN, D2HGDH) were ultimately obtained through random forest feature selection. Cox regression analysis confirmed the 6-gene signature is an independent prognostic factor in HNSCC patients. This signature effectively stratified samples in the training, test, and external verification sets (P < 0.01). The 5-year survival AUC in the training and verification sets was greater than 0.74. Thus, we have constructed a 6-gene signature as a new prognostic marker for predicting survival of HNSCC patients.

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