Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31
            <sup>comet</sup>

Eytan, Esther; Wang, Kexi; Miniowitz-Shemtov, Shirly; Sitry-Shevah, Danielle; Kaisari, Sharon; Yen, Tim J.; Liu, Song‐Tao; Hershko, Avram

doi:10.1073/pnas.1412901111

Cited by 112 publications

(141 citation statements)

References 30 publications

(67 reference statements)

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“…These results clearly demonstrate that maintenance of the SAC is critical to prevent cancer formation. TRIP13 has been shown to promote the dissociation of the MCC complex (15)(16)(17), which subsequently inactivates the SAC to prevent the completion of mitosis (18). Thus, overexpression of TRIP13 and silencing of MCC components have similar effects on cells, since both can lead to dysregulation of the SAC.…”

Section: Discussionmentioning

confidence: 99%

“…TRIP13 forms a stable hexameric ring, and ATP binding, as well as ATP hydrolysis, are critical for the function of the protein (13). Previous studies have revealed that TRIP13 is a novel component of the spindle assembly checkpoint (SAC) pathway (14)(15)(16)(17), which is crucial for the accurate distribution of duplicated chromosomes (18). Defects in the SAC pathway induce failure in chromosome separation and result in aneuploidy, which eventually leads to cellular apoptosis or transformation (19).…”

Section: Introductionmentioning

confidence: 99%

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TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

et al. 2016

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Abstract. Thyroid hormone receptor interactor 13 (TRIP13) is a member of the ATPases associated with various cellular activities family of proteins and is highly conserved in a wide range of species. Recent studies have demonstrated that TRIP13 is critical for the inactivation of the spindle assembly checkpoint and is associated with the progression of certain cancers. In the present study, the role of TRIP13 in colorectal cancer (CRC) was examined. Reverse transcription-quantitative polymerase chain reaction analysis revealed that TRIP13 messenger RNA was highly expressed in multiple CRC tissues. The depletion of TRIP13 in CRC cells suppressed cell proliferation, migration and invasion. To determine whether the catalytic activity of TRIP13 was critical for cancer progression, an inactive mutant of TRIP13 was expressed in CRC cells. The invasion of cancer cells that expressed the mutant TRIP13 was significantly reduced compared with that of the wild type TRIP13-expressing cancer cells. These results indicate that TRIP13 could be a potential target for CRC treatment. IntroductionThe ATPases associated with various cellular activities (AAA+) family of proteins comprises a functionally different group of enzymes that are involved in an array of cellular processes, including protein degradation, protein-complex disassembly and DNA replication (1). The AAA+ proteins are present in all kingdoms, and are characterized by the presence of conserved AAA+ domains that contain Walker A and Walker B motifs, followed by a conserved region called second region of homology (2). The majority of AAA+ proteins form hexamers to exert their biological functions. The chemical energy generated by adenosine triphosphate (ATP) hydrolysis by this family of proteins induces conformational changes in the substrate proteins to modulate their functions (3,4).A previous study reported that certain AAA+ enzymes are associated with tumor progression (5). For example, reptin [also known as RuvB-like (RUVBL) 2] and pontin (RUVBL1) have been demonstrated to be overexpressed in several tumors (5). These proteins interact with c-Myc or β-catenin, thus modulating their transcriptional activities to promote tumor progression (6). AAA+ proteins hydrolyze ATP, and thus, chemical inhibitors that disrupt the activities of cancer-associated AAA+ proteins may represent promising anti-cancer drugs.Thyroid hormone receptor interactor 13 (TRIP13, also known as 16E1BP and pachytene checkpoint 2) is a member of the AAA+ family proteins and is conserved in a wide range of species (7). It was first identified as a protein that interacts with human papilloma virus E1 proteins by a yeast two-hybrid analysis, but the physiological function of the interaction remains unknown (7). Accumulating studies have demonstrated that TRIP13 plays pivotal roles in meiotic recombination and DNA repair in plants, yeast, worms and mice (8-12). TRIP13 forms a stable hexameric ring, and ATP binding, as well as ATP hydrolysis, are critical for the function of the protein (13). Previous...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

et al. 2016

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“…In addition, TRIP13 and p31 comet promoted the inactivation of the mitotic checkpoint (30). However, the function of SAC-related proteins in mitosis has not yet been tested in plants, and several SAC proteins have been found to be involved in plant meiosis, such as MPS1, Aurora kinases, AtPCH2, and CDC20.1 in Arabidopsis, as well as CRC1 and BRK1 in rice (12,37).…”

Section: Discussionmentioning

confidence: 99%

“…The crystal structure of Mad2-p31 comet dimer was analyzed, and p31 comet was considered to mimic the structure of Mad2 to inhibit the dimerization of Mad2, allowing the metaphase/anaphase transition during mitotic checkpoint inactivation (29). Recent studies have shown that TRIP13 links p31 comet to disassemble the mitotic checkpoint complex (MCC) (30,31).…”

Section: Significancementioning

confidence: 99%

P31 ^comet , a member of the synaptonemal complex, participates in meiotic DSB formation in rice

Tang

Shen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The human mitotic arrest-deficient 2 (Mad2) binding protein p31 comet participates in the spindle checkpoint and coordinates cell cycle events in mitosis although its function in meiosis remains unknown in all organisms. Here, we reveal P31 comet as a synaptonemal complex (SC) protein in rice (Oryza sativa L.). In p31 comet , homologous pairing and synapsis are eliminated, leading to the homologous nondisjunction and complete sterility. The failure in loading of histone H2AX phosphorylation (γH2AX) in p31 comet , together with the suppressed chromosome fragmentation in rice completion of meiotic recombination 1 (com1) p31 comet and radiation sensitive 51c (rad51c) p31 comet double mutants, indicates that P31 comet plays an essential role in double-strand break (DSB) formation. Interestingly, the dynamic colocalization pattern between P31 comet and ZEP1 (a transverse filament protein of SC) by immunostaining, as well as the interaction between P31 comet and CENTRAL REGION COMPONENT 1 (CRC1) in yeast two-hybrid assays, suggests possible involvement of P31 comet in SC installation. Together, these data indicate that P31 comet plays a key role in DSB formation and SC installation, mainly through its cooperation with CRC1.uring meiosis, homologous recombination plays a crucial role in ensuring faithful and precise chromosome segregation, as well as in diversifying genetic information. Meiotic recombination is induced by the programmed formation of DNA double-strand breaks (DSBs), catalyzed by Spo11, a functional homolog of subunit A of an archaeal topoisomerase (TopoVIA) (1). In Saccharomyces cerevisiae, nine associated proteins, including meiotic recombination 11 (Mre11), radiation sensitive 50 (Rad50), X-ray sensitive 2 (Xrs2), superkiller 8 (Ski8), Rec102, Rec104, Rec114, meiosis-specific 4 (Mei4), and Mer2, are required for facilitating Spo11's catalytic reaction (2). In Schizosaccharomyces pombe, seven DSB formation-related proteins were identified (3). Rec6 has been recognized as an essential component for ensuring the meiotic DSB formation, and it forms a complex with Rec12 and Rec14, the orthologs of Spo11 and Ski8, respectively (4). Furthermore, the Mde2 protein, which lacks an ortholog in S. cerevisiae, is also required for DSB formation (5). Nevertheless, Rad50, Mre11, and Xrs2 orthologs are dispensable for DSB formation in S. pombe, as well as in mice and plants, but they are required for meiotic DSB processing (6). In mice, except for the conserved protein Spo11, Mei4 and Rec114 were also identified as key components involved in DSB formation (7). In addition, Mei1 was recognized as a recombination related factor, without an ortholog in S. cerevisiae or S. pombe (8). Recently, mouse TOPOVIBL protein was identified to form the complex with Spo11 and take part in meiotic DSB formation (9).In plants, the Arabidopsis AtSPO11-1, AtSPO11-2, and AtSPO11-3 share sequence similarity with other Spo11/topo VIA proteins. AtSPO11-1 and AtSPO11-2, as subunits of a heterodimer, are essential for DSB formation whereas A...

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“…But recent attention has focused on mutual inhibition between the MCC and the APC/C (Reddy et al 2007), which requires a particular APC/C subunit, APC15 (Mansfeld et al 2011;Foster and Morgan 2012;Uzunova et al 2012). In animal cells, a second important player for MCC disassembly is the p31 comet protein (Habu et al 2002;Teichner et al 2011;Westhorpe et al 2011), which has recently been implicated in targeting an AAA ATPase to the MCC to initiate its disassembly (Eytan et al 2014;Wang et al 2014).…”

Section: The Biochemistry Of Mitosismentioning

confidence: 99%

The Biochemistry of Mitosis

Wieser

Pines

2015

Cold Spring Harb Perspect Biol

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In this article, we will discuss the biochemistry of mitosis in eukaryotic cells. We will focus on conserved principles that, importantly, are adapted to the biology of the organism. It is vital to bear in mind that the structural requirements for division in a rapidly dividing syncytial Drosophila embryo, for example, are markedly different from those in a unicellular yeast cell. Nevertheless, division in both systems is driven by conserved modules of antagonistic protein kinases and phosphatases, underpinned by ubiquitin-mediated proteolysis, which create molecular switches to drive each stage of division forward. These conserved control modules combine with the self-organizing properties of the subcellular architecture to meet the specific needs of the cell. Our discussion will draw on discoveries in several model systems that have been important in the long history of research on mitosis, and we will try to point out those principles that appear to apply to all cells, compared with those in which the biochemistry has been specifically adapted in a particular organism.

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Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31 ^comet

Cited by 112 publications

References 30 publications

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

P31 ^comet , a member of the synaptonemal complex, participates in meiotic DSB formation in rice

The Biochemistry of Mitosis

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Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31 comet

Cited by 112 publications

References 30 publications

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

P31 comet , a member of the synaptonemal complex, participates in meiotic DSB formation in rice

The Biochemistry of Mitosis

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Product

Resources

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Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31 ^comet

P31 ^comet , a member of the synaptonemal complex, participates in meiotic DSB formation in rice