TTK kinase is essential for the centrosomal localization of TACC2

Dou, Zhen; Ding, Xia; Zereshki, Arzhang; Zhang, Ying; Zhang, Jie; Wang, Feng; Sun, Jie; Huang, He; Yao, Xuebiao

doi:10.1016/j.febslet.2004.06.092

Cited by 26 publications

(17 citation statements)

References 22 publications

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“…We therefore suggest this is because in normal conditions appropriate expression of TEIF may be necessary to ensure the homeostasis of centrosomes, whereas its overexpression is a dominant event in spontaneous tumorigenesis. Similar mechanics of operation have in fact been identified in other centrosomal factors such as TACC, cep135, Nek2 or Aurora A kinase (Ohta et al, 2002;Stenoien et al, 2003;Dou et al, 2004;Lou et al, 2004;Peset and Vernos, 2008).…”

Section: Discussionmentioning

confidence: 83%

“…For instance, the classic centrosome protein TACC2 and some regulators such as Erk2, p53 and BRCA1 distribute into centrosomes after phosphorylation (Dou et al, 2004;Lou et al, 2004;McPherson et al, 2006). However, in contrast to the putative N-terminal STYKc (Ser/Thr/Tyr) kinase-like domain, the C terminus of TEIF has no conserved functional domains shared with proteins in either the centrosome or other compartments.…”

Section: Discussionmentioning

confidence: 98%

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Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers

et al. 2009

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers

et al. 2009

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“…Other microtubule-related proteins were observed including Axin and TTK, which are known to play a role in microtubule dynamics. TTK is localized to the centrosome and is known to phosphorylate TACC2 (18). We showed that TACC2 is up-regulated as a result of SMYD2 overexpression (see below).…”

Section: Methodsmentioning

confidence: 89%

The Tale of Two Domains

Abu‐Farha

Lambert

Madhoun

et al. 2008

Molecular & Cellular Proteomics

179

105

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Very little is known about SET-and MYND-containing protein 2 (SMYD2), a member of the SMYD protein family. However, the interest in better understanding the roles of SMYD2 has grown because of recent reports indicating that SMYD2 methylates p53 and histone H3. In this study, we present a combined proteomics and genomics study of SMYD2 designed to elucidate its molecular roles. We report the cytosolic and nuclear interactome of SMYD2 using a combination of immunoprecipitation coupled with high throughput MS, chromatin immunoprecipitation coupled with high throughput MS, and co-immunoprecipitation methods. In particular, we report that SMYD2 interacted with HSP90␣ independently of the SET and MYND domains, with EBP41L3 through the MYND domain, and with p53 through the SET domain. We demonstrated that the interaction of SMYD2 with HSP90␣ enhances SMYD2 histone methyltransferase activity and specificity for histone H3 at lysine 4 (H3K4) in vitro. Interestingly histone H3K36 methyltransferase activity was independent of its interaction with HSP90␣ similar to LSD1 dependence on the androgen receptor. We also showed that the SET domain is required for the methylation at H3K4. We demonstrated using a modified chromatin immunoprecipitation protocol that the SMYD2 gain of function leads to an increase in H3K4 methylation in vivo, whereas no observable levels of H3K36 were detected. We also report that the SMYD2 gain of function was correlated with the upregulation of 37 and down-regulation of four genes, the majority of which are involved in the cell cycle, chromatin remodeling, and transcriptional regulation. TACC2 is one of the genes up-regulated as a result of SMYD2 gain of function. Up-regulation of TACC2 by SMYD2 occurred as a result of SMYD2 binding to the TACC2 promoter where it methylates H3K4. Furthermore the combination of the SMYD2 interactome with the gene expression data suggests that some of the genes regulated by SMYD2 are closely associated with SMYD2-interacting proteins. Molecular & Cellular Proteomics 7:560 -572, 2008.The mapping of protein-protein interaction helps us understand the function of proteins. In recent years, our group (1) and others (2, 3) have performed protein interaction experiments for large sets of human proteins. Our approach for the mapping of protein-protein interactions is based on immunoprecipitation coupled with high throughput MS (IP-HTMS). 1The SMYD protein family consists of five proteins (SMYD1-5) that are not fully characterized and are grouped based on the presence of two conserved domains (MYND and SET domains). The MYND domain is a zinc finger motif that is involved in protein-protein interaction. It is named after Myeloid, Nervy, and DEAF-1, which are the three most characterized proteins that contain the MYND domain (4). The SET domain is an evolutionarily conserved sequence motif consisting of 130 -140 amino acids. Its name is derived from the three proteins in which it was initially characterized: Su (var) 3-9, Enhancer-of-zeste, and Trithorax (5, 6). These enzymes a...

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“…Given the interaction between CENP-E and Mps1/TTK and the essential role of TTK/Mps1 kinase activity for CENP-E distribution to the kinetochore (31,32), it is tempting to speculate that TTK/Mps1 phosphorylates CENP-E and triggers its plus-end-directed kinesin motility essential for its translocation to the kinetochore in mitosis. This speculation becomes even more plausible given the fact that a decrease of ATP level is correlated to the departure of CENP-E from the kinetochore to the pole (33).…”

Section: Discussionmentioning

confidence: 99%

Septin 7 Interacts with Centromere-associated Protein E and Is Required for Its Kinetochore Localization

Zhu

Wang

Yan

et al. 2008

Journal of Biological Chemistry

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Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore. Septin (SEPT) belongs to a conserved family of polymerizing GTPases localized to the metaphase spindle during mitosis. Previous study showed that SEPT2 depletion results in chromosome mis-segregation correlated with a loss of centromere-associated protein E (CENP-E) from the kinetochores of congressing chromosomes (1). However, it has remained elusive as to whether CENP-E physically interacts with SEPT and how this interaction orchestrates chromosome segregation in mitosis. Here we show that SEPT7 is required for a stable kinetochore localization of CENP-E in HeLa and MDCK cells. SEPT7 stabilizes the kinetochore association of CENP-E by directly interacting with its C-terminal domain. The region of SEPT7 binding to CENP-E was mapped to its C-terminal domain by glutathione S-transferase pull-down and yeast two-hybrid assays. Immunofluorescence study shows that SEPT7 filaments distribute along the mitotic spindle and terminate at the kinetochore marked by CENP-E. Remarkably, suppression of synthesis of SEPT7 by small interfering RNA abrogated the localization of CENP-E to the kinetochore and caused aberrant chromosome segregation. These mitotic defects and kinetochore localization of CENP-E can be successfully rescued by introducing exogenous GFP-SEPT7 into the SEPT7-depleted cells. These SEPT7-suppressed cells display reduced tension at kinetochores of bi-orientated chromosomes and activated mitotic spindle checkpoint marked by Mad2 and BubR1 labelings on these misaligned chromosomes. These findings reveal a key role for the SEPT7-CENP-E interaction in the distribution of CENP-E to the kinetochore and achieving chromosome alignment. We propose that SEPT7 forms a link between kinetochore distribution of CENP-E and the mitotic spindle checkpoint.Chromosome movements during mitosis are governed by the interaction of spindle microtubules with a specialized chromosome domain located within the centromere. This specialized region, called the kinetochore (2), is the site for spindle microtubule-centromere association. In addition to providing a physical link between chromosomes and spindle microtubules, the kinetochore plays an active role in chromosomal segregation through microtubule motors and spindle checkpoint sensors located at or near it (3). During mitosis, attaching, positioning, and bi-orientating, kinetochores with the spindle microtubules play essential roles in chromosome segregation and genomic stability.CENP-E 3 is a microtubule-based kinesin motor protein located on the outer kinetochore and is involved in a stable microtubule-kinetochore attachment (4). CENP-E participates in the chromosome movements from prometaphase to anaphase (5) by tethering the kinetochores to microtubule "plus" ends and moving toward the equator (3, 6), thereby helping mono-oriented chromosomes align at the metaphase plate before bi-orientation (7). A recent study showed that the mammalian septin network coop...

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TTK kinase is essential for the centrosomal localization of TACC2

Cited by 26 publications

References 22 publications

Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers

Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers

The Tale of Two Domains

Septin 7 Interacts with Centromere-associated Protein E and Is Required for Its Kinetochore Localization

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