CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis

Huang, Yunpeng; Wang, Wenwen; Yao, Phil; Wang, Xiwei; Liu, Xing; Zhuang, Xiaoxuan; Yan, Feng; Zhou, Jinhua; Du, Jinyan; Ward, Tarsha; Zou, Hanfa; Zhang, Jiancun; Fang, Guowei; Ding, Xia; Dou, Zhen; Yao, Xuebiao

doi:10.1074/jbc.m111.277194

Cited by 48 publications

(67 citation statements)

References 40 publications

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“…A recent study speculates that the SKAP⅐Astrin complex localizes and regulates microtubule plus-ends (13). Our investigation of protein networks interacting with CENP-E has led to the identification of SKAP-CENP-E interaction (14). Our study showed that SKAP cooperates with CENP-E to orchestrate kinetochore-microtubule interaction for faithful chromosome segregation (14).…”

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confidence: 90%

“…Plasmids and Recombinant Protein Production-The fulllength SKAP mRNA was amplified as described previously (14). GFP-tagged SKAP full-length and deletion truncations were cloned into pEGFP-C2 (Clontech).…”

Section: Methodsmentioning

confidence: 99%

“…Our study showed that SKAP cooperates with CENP-E to orchestrate kinetochore-microtubule interaction for faithful chromosome segregation (14). Interestingly, suppression of CENP-E does not abolish the kinetochore localization of SKAP (14), raising interest in the identification of the kinetochore constituent(s) that specifies SKAP localization to the kinetochore.…”

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confidence: 99%

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Mitotic Regulator SKAP Forms a Link between Kinetochore Core Complex KMN and Dynamic Spindle Microtubules

Wang

Zhuang

Cao

et al. 2012

Journal of Biological Chemistry

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Background: KMN (KNL/MIS12/NDC80) is a kinetochore constituent essential for chromosome movements in mitosis. Results: KMN protein specifies the kinetochore localization of SKAP. SKAP regulates spindle microtubule dynamics for accurate chromosome movements. Conclusion: The MIS13-SKAP interaction links kinetochore structural components to dynamic microtubule plus-ends. Significance: MIS13-SKAP interaction governs chromosome dynamics and stability in mitosis.

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confidence: 90%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Mitotic Regulator SKAP Forms a Link between Kinetochore Core Complex KMN and Dynamic Spindle Microtubules

Wang

Zhuang

Cao

et al. 2012

Journal of Biological Chemistry

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“…As shown in Fig. 2D, right panel, lanes [15][16][17][18], Western blotting analyses with a monoclonal antibody of GFP demonstrated that the GFP fusion proteins containing the C-terminal TIP150, in addition to full-length GFP-TIP150, were readily retained on GST-CTN matrix. The N-terminal domain also exhibited weak binding activity toward CTN (Fig.…”

Section: Identification Of a Novel Tip150-ctn Complex In Interphasementioning

confidence: 99%

“…Because TIP150 protein levels remain unchanged during the cell cycle, we sought to examine the role of TIP150 in interphase cells. To study the molecular association of TIP150 with other microtubule end-binding proteins, we carried out an affinity isolation of a TIP150-containing protein complex followed by mass spectrometric identification of tryptic peptides derived from the individually sliced bands as described previously (17,18). As shown in Fig.…”

Section: Identification Of a Novel Tip150-ctn Complex In Interphasementioning

confidence: 99%

The Microtubule Plus End Tracking Protein TIP150 Interacts with Cortactin to Steer Directional Cell Migration

Adams

Zhang

Wang

et al. 2016

Journal of Biological Chemistry

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Cell migration is orchestrated by dynamic interactions of microtubules with the plasma membrane cortex. How these interactions facilitate these dynamic processes is still being actively investigated. TIP150 is a newly characterized microtubule plus end tracking protein essential for mitosis and entosis (Ward, T., Wang, M., Liu, X., Wang, Z., Xia, P., Chu, Y., Wang, X., Liu, L., Jiang, K., Yu, H., Yan, M., Wang, J., Hill, D. L., Huang, Y., Zhu, T., and Yao, X. (2013) Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis. J. Biol. Chem. 288, 15771-15785; Xia, P., Zhou, J., Song, X., Wu, B., Liu, X., Li, D., Zhang, S., Wang, Z., Yu, H., Ward, T., Zhang, J., Li, Y., Wang, X., Chen, Y., Guo, Z., and Yao, X. (2014) Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction. J. Mol. Cell Biol. 6, 240 -254). Here we show that TIP150 links dynamic microtubules to steer cell migration by interacting with cortactin. Mechanistically, TIP150 binds to cortactin via its C-terminal tail. Interestingly, the C-terminal TIP150 proline-rich region (CT150) binds to the Src homology 3 domain of cortactin specifically, and such an interaction is negatively regulated by EGF-elicited tyrosine phosphorylation of cortactin. Importantly, suppression of TIP150 or overexpression of phospho-mimicking cortactin inhibits polarized cell migration. In addition, CT150 disrupts the biochemical interaction between TIP150 and cortactin in vitro, and perturbation of the TIP150-cortactin interaction in vivo using a membrane-permeable TAT-CT150 peptide results in an inhibition of directional cell migration. We reason that a dynamic TIP150-cortactin interaction orchestrates directional cell migration via coupling dynamic microtubule plus ends to the cortical cytoskeleton.Cell migration is an essential physiological function that is tightly regulated in numerous biological processes, including development, tissue remodeling, wound healing, and tumor metastasis (1, 2). These processes require coordination of dynamic reorganization between the actin filaments and microtubules.Cortactin (CTN) 6 is a multidomain-containing scaffold protein that consists of an N-terminal acidic domain, six and a half tandem repeats, an ␣ helix, a proline-rich region, and an Src Homology (SH3) domain at its C terminus (3). CTN is an important scaffold for promoting the polymerization and rearrangement of the actin cytoskeleton (4). Functionally, CTN, distributed at protrusions and the leading edges, is necessary for cell migration by regulating intercellular adhesion and cell spreading (5). Importantly, CTN is phosphorylated at tyrosine residues in response to growth factor receptors, which regulates cell migration (6).Microtubules, one of the three major components of the cytoskeleton, are required for maintaining the physical and plastic properties of migrating cells (7). The plus en...

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Mapping the kinetochore MAP functions required for stabilizing microtubule attachments to chromosomes during metaphase

2019

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In mitosis, faithful chromosome segregation is orchestrated by the dynamic interactions between the spindle microtubules (MTs) emanating from the opposite poles and the kinetochores of the chromosomes. However, the precise mechanism that coordinates the coupling of the kinetochore components to dynamic MTs has been a long‐standing question. Microtubule‐associated proteins (MAPs) regulate MT nucleation and dynamics, MT‐mediated transport and MT cross‐linking in cells. During mitosis, MAPs play an essential role not only in determining spindle length, position, and orientation but also in facilitating robust kinetochore‐microtubule (kMT) attachments by linking the kinetochores to spindle MTs efficiently. The stability of MTs imparted by the MAPs is critical to ensure accurate chromosome segregation. This review primarily focuses on the specific function of nonmotor kinetochore MAPs, their recruitment to kinetochores and their MT‐binding properties. We also attempt to synthesize and strengthen our understanding of how these MAPs work in coordination with the kinetochore‐bound Ndc80 complex (the key component at the MT‐binding interface in metaphase and anaphase) to establish stable kMT attachments and control accurate chromosome segregation during mitosis.

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CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis

Cited by 48 publications

References 40 publications

Mitotic Regulator SKAP Forms a Link between Kinetochore Core Complex KMN and Dynamic Spindle Microtubules

Mitotic Regulator SKAP Forms a Link between Kinetochore Core Complex KMN and Dynamic Spindle Microtubules

The Microtubule Plus End Tracking Protein TIP150 Interacts with Cortactin to Steer Directional Cell Migration

Mapping the kinetochore MAP functions required for stabilizing microtubule attachments to chromosomes during metaphase

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