Table of Contents

Volume 8, Issue 2

  January 15, 2009

  Pages 183 - 329

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NEWS & VIEWS

Open Access Article

A new year, a new role for p21: Mediating degradation of Cyclin B1

Angela Tyner
Pages 183 - 184
http://dx.doi.org/10.4161/cc.8.2.7824
PDF

Open Access Article

Survivin(g) phosphorylation? Survivin phosphorylation, mitosis and apoptosis

Patrick Eyers
Pages 183 - 184
http://dx.doi.org/10.4161/cc.8.2.7828
PDF

Open Access Article

New TGF-β and Ras crosstalk in EMT

Jiri Zavadil
Pages 183 - 184
http://dx.doi.org/10.4161/cc.8.2.7830
PDF




EXTRA VIEWS

Open Access Article

The ubiquitin-selective chaperone CDC-48/p97, a new player in DNA replication

Alexandra Deichsel, Julien Mouysset and Thorsten Hoppe
Pages 185 - 190
http://dx.doi.org/10.4161/cc.8.2.7356
Abstract | PDF

Efficient duplication of the genome and its equal distribution into both daughter cells is an essential process for all dividing organisms. To ensure that DNA replication occurs only once during the S phase of the cell cycle, initiation of replication is tightly controlled. Initiation factors are responsible for the recruitment of the replisome, the large molecular machine carrying out DNA synthesis, to origins of replication and license them to start DNA duplication. Remarkably, most of the currently known initiators have been classified as members of the family of AAA+ ATPases.¹ In our recent study we identified an additional AAA+ ATPase, CDC-48, to be essential for proper DNA replication in Caenorhabditis elegans.² Here, we speculate on the function of CDC-48 (also known as Cdc48p in yeast and p97 in vertebrates) during DNA replication initiation, addressing its ubiquitin-selective chaperone activity.

Open Access Article

Dual functions of DNA replication forks in checkpoint signaling and PCNA ubiquitination

Xiaohong H. Yang and Lee Zou
Pages 191 - 194
http://dx.doi.org/10.4161/cc.8.2.7357
Abstract | PDF

During cell proliferation, DNA damage inflicted by intrinsic or extrinsic genotoxic stresses impose a thereat to DNA replication. The stability of the DNA replication forks that encounter DNA damage is crucial for genomic integrity. Both the ATR-regulated checkpoint pathway and the translesion DNA synthesis mediated by the ubiquitinated PCNA are important for continuous replication of damaged DNA. We have recently shown that Chk1, a key effector kinase of ATR in checkpoint response, is required for efficient PCNA ubiquitination after DNA damage. Surprisingly, the ubiquitination of PCNA is independent of ATR, but regulated by Claspin, a replication protein that mediates the activation of Chk1 by ATR. Like Claspin, Timeless and Rad17, two other Chk1 regulators at stressed replication forks, are also implicated in PCNA ubiquitination. These findings suggest that while ATR signaling and PCNA ubiquitination are two independent processes, they are mediated by a common group of proteins including Chk1 and it regulators at replication forks. Furthermore, these data raise the possibility that Chk1 and its regulators may constitute a functional module at replication forks to enable multiple stress responses.

Open Access Article

Reuse, replace, recycle: Specificity in subunit inheritance and assembly of higher-order septin structures during mitotic and meiotic division in budding yeast

Michael A. McMurray and Jeremy W. Thorner
Pages 195 - 203
http://dx.doi.org/10.4161/cc.8.2.7381
Abstract | PDF

Septins are guanine nucleotide-binding proteins that form hetero-oligomeric complexes, which assemble into filaments and higher-order structures at sites of cell division and morphogenesis in eukaryotes.  Dynamic changes in the organization of septin-containing structures occur concomitantly with progression through the mitotic cell cycle and during cell differentiation.  Septins also undergo stage-specific post-translational modifications, which have been implicated in regulating their dynamics, in some cases via purported effects on septin turnover.  In our recent study, the fate of two of the five septins expressed in mitotic cells of budding yeast (Saccharomyces cerevisiae) was tracked using two complementary fluorescence-based methods for pulse-chase analysis.  During mitotic growth, previously-made molecules of both septins (Cdc10 and Cdc12) persisted through multiple successive divisions and were incorporated equivalently with newly synthesized molecules into hetero-oligomers and higher-order structures.  Similarly, in cells undergoing meiosis and the developmental program of sporulation, pre-existing copies of Cdc10 were incorporated into new structures.  In marked contrast, Cdc12 was irreversibly excluded from septin complexes and replaced by another septin, Spr3.  Here, we discuss the broader implications of these results and related findings with regard to how septin dynamics is coordinated with the mitotic cell cycle and in the yeast life cycle, and how these observations may relate to control of the dynamics of other complex multi-subunit assemblies.

Open Access Article

The translation initiation factor DAP5 is a regulator of cell survival during mitosis

Noa Liberman, Lea Marash and Adi Kimchi
Pages 204 - 209
http://dx.doi.org/10.4161/cc.8.2.7384
Abstract | PDF

Initiation of protein translation is tightly regulated by various physiological signals and involves cap-dependent and independent mechanisms. DAP5 protein is an eIF4G family member previously implicated in mediating cap-independent IRES driven translation in response to various cellular stresses. Unexpectedly, we have recently found that DAP5 is also essential for continuous cell survival in non-stressed cells. We reported in this respect that the knock down of endogenous DAP5 by RNA-interference induces M-phase specific caspase-dependent cell death. Bcl-2 and CDK1 were identified as DAP5 mRNA targets, the translation of which was selectively reduced in the DAP5 knocked down cells. They each possess functional IRES element in their 5'UTR. Here we review the major results of this study and present new data on the link of DAP5 to additional Bcl-2 family members. In addition we discuss other possible cellular phenotypes resulting from the knock down of DAP5 in these cells.

Open Access Article

Fine-tuning of nuclear β-catenin by Chibby and 14-3-3

Ken-Ichi Takemaru, Victoria Fischer and Feng-Qian Li
Pages 210 - 213
http://dx.doi.org/10.4161/cc.8.2.7394
Abstract | PDF

Chibby (Cby) is an evolutionarily conserved antagonist of β -catenin, a central player of the canonical Wnt signaling pathway, which acts as a transcriptional coactivator. Cby physically interacts with the C-terminal activation domain of β -catenin and blocks its transcriptional activation potential through competition with DNA-binding Tcf/Lef transcription factors. Our recent study revealed a second mechanism for Cby-mediated β -catenin inhibition in which Cby cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of β -catenin, following phosphorylation of Cby by Akt kinase. Therefore, our findings unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplamic trafficking of β -catenin and provide new insights into the cross-talk between the Wnt and Akt signaling pathways. Here, we review recent literature concerning Cby function and discuss our current understanding of the relationship between Wnt and Akt signaling.

Open Access Article

All eukaryotes: Before turning off G₁-S transcription, please check your DNA

Robertus A.M. de Bruin and Curt Wittenberg
Pages 214 - 217
http://dx.doi.org/10.4161/cc.8.2.7412
Abstract | PDF

The DNA replication and DNA damage checkpoints are required for the efficient response to genotoxic stress, which is critical for genome stability and cell survival. The DNA replication and damage checkpoints delay progression into mitosis, and at the same time induce the transcription of genes that promote repair of cellular lesions including stabilization of stalled replication forks and induction of DNA repair functions. The elucidation of the mechanism by which the DNA replication checkpoint activates transcription of G1/S genes is provided by our recent study reported in the August issue of Proceedings of the National Academy of Sciences. We show that, in response to stimulation of the DNA replication checkpoint, activation of G1-S transcription is established by inactivation, via phosphorylation by the checkpoint protein kinases, of the MBF-associated transcriptional corepressor Nrm1. This regulation is critical for the survival of cells responding to genotoxic stress. This provides a simple but elegant mechanism by which checkpoint activation can override the regular periodic transcriptional program by directly regulating a cell cycle dependent transcriptional repressor. We discuss the likely conservation of this regulatory pathway in yeast and man.




PERSPECTIVES

Open Access Article

Gene fusions and RNA trans-splicing in normal and neoplastic human cells

Hui Li, Jinglan Wang, Xianyong Ma and Jeffrey Sklar
Pages 218 - 222
http://dx.doi.org/10.4161/cc.8.2.7358
Abstract | PDF

Chimeric gene products, most often resulting from chromosome translocations, have been considered unique features of cancer, or at least of cells at high risk for becoming cancerous. Chimeric JAZF1-JJAZ1 mRNA transcribed from DNA spanning the site of recombination in the (7;17)(p15;q21) chromosomal translocation found in half of endometrial stromal sarcomas and most cases of benign stromal nodules is one such example.  The recent finding that chimeric JAZF1-JJAZ1 mRNA can also be detected in normal endometrial stromal cells suggests that chimeric gene products are not limited to cancer or pre-cancerous cells.  The JAZF1-JJAZ1 mRNA and the protein encoded by it appear to be identical to that synthesized from the gene fusion in neoplastic cells.  In cultured cells, the chimeric protein has anti-apoptotic properties and is pro-proliferative when unrearranged JJAZ1 alleles are silenced, as they are in endometrial stromal sarcomas but not in the stromal nodules.  These observations are consistent with the conclusion that chromosomal rearrangements and gene fusions in neoplastic cells may represent mechanisms for the deregulated expression of chimeric gene products that are generated at specific stages in cell development and have physiologic functions in normal cells.  Furthermore, it may be possible that other means for abnormal production of chimeric gene products, such as hyperactive trans-splicing of RNA, may be another mechanism underlying the neoplastic properties of tumor cells.

Open Access Article

Replication checkpoint control by a PTK/STAT3/Cyclin D1 axis

Ben J. Shields and Tony Tiganis
Pages 223 - 230
http://dx.doi.org/10.4161/cc.8.2.7382
Abstract | PDF

Tyrosine phosphorylation-dependent signalling, controlled by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is typically associated with the cellular response to mitogens in G1. However, a growing number of studies indicate that PTKs and PTPs can have important roles in cellular division beyond this initial phase of the cell cycle.  In this Perspective we discuss the impact and contributions of PTKs and PTPs to cell cycle checkpoints.  We focus on the replication checkpoint and our recent findings that demonstrate that the attenuation of PTK-mediated STAT3 signalling for the depletion of cyclin D1, works in concert with ATR-instigated cascades for the suppression of S-phase progression. We argue for the need for integrated responses and highlight the potential for oncogenic PTK pathways to bypass the replication checkpoint and contribute to genomic instability.

Open Access Article

Spatial signaling networks converge at the adaptor protein Shc

Daniel Timothy Sweet and Ellie Tzima
Pages 231 - 235
http://dx.doi.org/10.4161/cc.8.2.7383
Abstract | PDF

Endothelial cells, which are located at the interface between the blood and the heart wall, respond dynamically to a variety of stimuli initiating signaling cascades that regulate cardiovascular development, physiology and pathology. These inputs include soluble factors that bind to their receptors, integrin-matrix interactions, cell-cell contacts and mechanical forces due to the flowing blood. While these stimuli can mediate unique downstream signals, it is well-accepted that signaling pathways are highly interwoven into complex signaling networks with several levels of cross-talk, integration and coordination. Recent studies suggest that several signaling networks coalesce at the adaptor protein Shc.

Open Access Article

Tumor endothelial cells have features of adult stem cells

Andrew C. Dudley and Michael Klagsbrun
Pages 236 - 238
http://dx.doi.org/10.4161/cc.8.2.7413
Abstract | PDF

We recently reported that prostate tumor-specific endothelial cells had features of mesenchymal stem cells and could trans-differentiate to form cartilage and bone-like tissues.  Plasticity in the tumor vasculature may be related to well-known tumor blood vessel abnormalities and could underlie an intrinsic adaptive mechanism in tumor endothelial cells for circumventing anti-angiogenic strategies.




REPORTS

Open Access Article

Bck2 is a phase-independent activator of cell cycle-regulated genes in yeast

Francisco Ferrezuelo, Martí Aldea and Bruce Futcher
Pages 239 - 252
http://dx.doi.org/10.4161/cc.8.2.7543
Abstract | PDF

During the cell division cycle of the yeast Saccharomyces cerevisiae, the G₁-to-S transition depends upon the activation of two transcription factors (SBF and MBF), which are responsible for the cell cycle-regulated expression of more than 200 genes. Bck2 becomes essential in the absence of Cln3, the most upstream activator of this transcriptional program. Here we have used a genome-wide approach to elucidate the targets of Bck2. Our data indicate that Bck2 activates a selection of cell cycle-regulated genes from all cell cycle stages. In contrast, Cln3 activates only G₁/S phase genes. Furthermore, Bck2 activates many genes independently of Swi6, the common component of SBF and MBF. Comparison of Bck2 targets with those of other transcription factors suggests that, in addition to SBF and MBF, Bck2 may elicit gene expression via Ste12 and Mcm1. We propose that Bck2 activates its targets by a mechanism fundamentally different from that of Cln3, and that it may be a necessary cofactor for the full expression of a subset of cell cycle-regulated genes.

Open Access Article

p21^Cip1/WAF1 mediates cyclin B1 degradation in response to DNA damage

Laura D. Gillis, Andrew M. Leidal, Richard Hill and Patrick W.K. Lee
Pages 253 - 256
http://dx.doi.org/10.4161/cc.8.2.7550
Abstract | PDF

p21^Cip1/WAF1 is the principle mediator of cell cycle arrest in response to DNA damage. p21 primarily mediates G₁ cell cycle arrest by inactivating G₁-associated cyclin A- and cyclin E-containing cyclin/cdk complexes. In the present study we investigate the role of p21 in DNA damage-induced G₂ cell cycle arrest, particularly with respect to the G₂-associated cyclin, cyclin B1. We demonstrate that cells lacking p21 or deficient in their ability to upregulate p21 are unable to mediate the downregulation of cyclin B1 in response to DNA damage as compared to wild-type cells. Decreased levels of cyclin B1 in response to DNA damage seen in wild-type cells is due to p21-mediated degradation of cyclin B1 as this can be inhibited by a proteasomal inhibitor. Cell cycle analysis reveals that p21-null cells are unable sustain G₂ cell cycle arrest and accumulate at greater than 4N DNA content. These results indicate that p21-mediated degradation of cyclin B1 in response to DNA damage is necessary for the maintenance of G₂ cell cycle arrest.

Open Access Article

Nek1 regulates cell death and mitochondrial membrane permeability through phosphorylation of VDAC1

Yumay Chen, William J. Craigen and Daniel J. Riley
Pages 257 - 267
http://dx.doi.org/10.4161/cc.8.2.7551
Abstract | PDF

The mammalian NIMA-related protein kinase 1 (Nek1) is important for keeping cells alive after DNA damage, but the mechanism by which injured cells die without functional Nek1 has not yet been demonstrated. Here we show that Nek1 regulates the pathway to mitochondrial cell death through phosphorylation of voltage dependent anion channel 1 (VDAC1) on serine 193. Nek1 associates with VDAC1 in a yeast two-hybrid system, as well as by GST pull-down assays and by reciprocal immunoprecipitation. A portion of Nek1 in cells also localizes at mitochondria. Ectopic expression of a kinase-dead Nek1 mutant results in cell death, which is immediately preceded by loss of the Nek1-dependent VDAC1-S193 phosphorylation. UV irradiation of Nek1-deficient cells or silencing of endogenous Nek1 expression similarly results in loss of the specific S193 phosphorylation before cells die. Nek1-deficient cells are characterized by exaggerated mitochondrial membrane permeability (MMP) and accelerated cell death. Ectopic expression of a VDAC1-Ser193Ala mutant, which cannot be phosphorylated by Nek1, also results in cell death. A VDAC1-Ser193Glu mutant, designed to mimic constitutive phosphorylation by Nek1, rescues exaggerated MMP and keeps cells alive after DNA damaging injury, but only transiently. The direct interaction between Nek1 and VDAC1 provides a mechanism to explain how Nek1 prevents excessive cell death, as well as the first direct evidence that a specific kinase regulates VDAC1 activity.

Open Access Article

Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARγ-dependent and PPARγ-independent pathways

Besstina E. Lyles, Tunde O. Akinyeke, Patrice E. Moss and LaMonica V. Stewart
Pages 268 - 277
http://dx.doi.org/10.4161/cc.8.2.7584
Abstract | PDF

Thiazolidinediones (TZDs) are peroxisome proliferator activated receptor gamma (PPARγ) ligands that have been reported to reduce proliferation of human prostate cancer cells.  However, the mechanisms by which TZDs inhibit prostate cancer cell proliferation are not fully understood.  In addition, it is not known if the anti-proliferative effects of TZDs require activation of PPARγ or are mediated by PPARγ –independent pathways.  The goals of this study were to assess whether TZDs regulate expression of proteins that control the transition from G1 to S phase of the cell cycle and define the role of PPARγ in these TZD-induced responses in androgen-independent human prostate cancer cell lines.  Western blot analysis revealed that growth inhibitory concentrations of the TZDs rosiglitazone and ciglitazone induced expression of the cyclin dependent kinase inhibitor p21 and decreased cyclin D1 levels in the androgen independent PC-3 cell line.  Phosphorylation of retinoblastoma protein at Serine 780 was also reduced in PC-3 cells exposed to ciglitazone.  Furthermore, growth inhibitory concentrations of ciglitazone increased p21 and lowered cyclin D1 expression within C4-2 cells. PPARγ-directed siRNAs inhibited the ability of rosiglitazone to regulate expression of cyclin D1 and p21.  However, knockdown of PPARγ did not significantly reduce ciglitazone-induced alterations in cyclin D1 and p21.  Furthermore PPARγ siRNA did not prevent inhibition of PC-3 cell proliferation by either TZD.   Thus, activation of PPARγ is involved in rosiglitazone-induced alterations in cell cycle protein expression. However, the alterations in protein expression and proliferation induced by ciglitazone occur primarily via PPARγ-independent signaling pathways.

Open Access Article

Phosphorylation of survivin at threonine 34 inhibits its mitotic function and enhances its cytoprotective activity

Rachel M.A. Barrett, Toby P. Osborne and Sally P. Wheatley
Pages 278 - 283
http://dx.doi.org/10.4161/cc.8.2.7587
Abstract | PDF

Survivin is an essential chromosomal passenger protein required for mitotic progression.  It is also an inhibitor of apoptosis and can prevent caspase-mediated cell death.  In addition, survivin levels are elevated in cancer cells where its presence correlates with increased resistance to chemo- and radio-therapy, which makes it an attractive target for novel anti-cancer strategies.  Interestingly, survivin is phosphorylated by the mitotic kinase, cdk1, and a non-phosphorylatable form, survivinT34A, cannot inhibit apoptosis. Here we rigorously test the ability of survivinT34A and its corresponding phosphomimetic, survivinT34E, to promote cell viability through survivin’s dual role. The effects of these mutations are diametrically opposed: survivinT34A accelerates cell proliferation and promotes apoptosis, whereas survivinT34E retards growth and promotes survival. Thus the phosphorylation status of survivin at T34 is pivotal to a cell’s decision to live or die.

Open Access Article

Ras alters epithelial-mesenchymal transition in response to TGF-β by reducing actin fibers and cell-matrix adhesion

Alfiya F. Safina, Andrea E. Varga, Anna Bianchi, Qiao Zheng, Dimiter Kunnev, Ping Liang and Andrei Bakin
Pages 284 - 298
http://dx.doi.org/10.4161/cc.8.2.7590
Abstract | PDF

TGF-β and Ras regulate epithelial-mesenchymal transition (EMT), a process that contributes to tumor invasion and metastasis. The interaction of these pathways in EMT is still poorly understood. Here, we show that TGF-β induces EMT but limits cell invasion whereas hyperactivated Ras (H-RasV12) does not cause EMT but enhances cell invasion, alleviating the inhibitory effect of TGF-β. TGF-β disrupts cell junctions and induces tropomyosin-mediated actin fibers and matrix adhesion. Smad transcription factors mediate both steps of the TGF-β-induced EMT whereas RasV12 inhibits the second step by blocking the induction of tropomyosins (TPM1) and reducing cell-matrix adhesion and integrin signaling. RasV12 prevents binding of Smads to the TPM1 promoter by forcing CRM1-dependent nuclear export of Smad4. Soft agar and animal studies demonstrate that RasV12 confers the metastatic potential in epithelial cells, whereas tropomyosin suppresses tumor growth and metastases. Thus, TGF-β-induced EMT is not sufficient for the acquisition of the invasive potential and activated Ras alters this TGF-β response, conferring the tumorigenic and invasive potential.

Open Access Article

Nitrosative stress suppresses checkpoint activation after DNA synthesis inhibition

Robert J. Tomko, Jr., Ndang N. Azang-Njaah and Celeste Reese
Pages 299 - 305
http://dx.doi.org/10.4161/cc.8.2.7595
Abstract | PDF

DNA synthesis is promoted by the dephosphorylation and activation of cyclin-dependent kinase 2 (Cdk2) complexes by Cdc25A.  Nitrosative stress suppresses Cdk2 dephosphorylation by Cdc25A in vitro and inhibits Cdc25A protein translation in cells, but the effects on S-phase progression remain unexamined.  Herein we report that nitrosative stress catalyzed by inducible nitric oxide (•NO) synthase (iNOS) or the chemical nitrosant S-nitrosocysteine ethyl ester (SNCEE) rapidly inhibited DNA synthesis concomitant with Cdc25A loss.  Surprisingly, this inhibition of DNA synthesis was refractory to ectopic expression of Cdc25A or a Cdc25-independent Cdk2 mutant.  Nitrosative stress inhibited DNA synthesis without activating checkpoint signaling, thus distinguishing it from S-phase arrest mediated by other reactive •NO-derived species.  The apparent lack of checkpoint activation was due to an active suppression because accumulation of pSer345-Chk1, pThr68-Chk2, and γH2AX was inhibited by nitrosative stress in cells exposed to DNA damage or replication inhibitors.  We speculate that failure to activate the S-phase checkpoint in precancerous cells undergoing nitrosative stress may elevate the risk of transmitting damaged genomes to daughter cells upon cell cycle reentry.

Open Access Article

Pro-apoptotic effect of aurothiomalate in prostate cancer cells

Marianna Trani, Alessandro Sorrentino, Christer Busch and Marene Landström
Pages 306 - 313
http://dx.doi.org/10.4161/cc.8.2.7596
Abstract | PDF

It has been recently demonstrated that small gold compounds could have a potential anti-tumoral activity. Here, we report that aurothiomalate (ATM), a gold compound already used in clinical therapy for the treatment of rheumatoid arthritis, has a pro-apoptotic effect in aggressive prostate cancer (PC3U) cells. In contrast, treatment of human primary epithelial prostate cells (PrEC) with ATM did not cause apoptosis. We demonstrated that ATM is able to disrupt the PKCι-Par6 complex in PC3U cells and that this disruption leads to the activation of ERK in a dose-dependent manner. Interestingly, we also showed that ERK acts upstream of the activation of caspase 3, leading to apoptosis. ATM treatment also causes activation of p38 and JNK MAP kinases. Moreover we could link ATM treatment to activation of the mitochondrial or so called intrinsic pathway, as we observed release of cytochrome c from mitochondria to cytoplasm, suggesting that the mitochondrial pathway is involved in the pro-apoptotic effect mediated by ATM. Taken together our data suggest that ATM could be a new promising drug for the treatment of advanced prostate cancer.

Open Access Article

TMAP/CKAP2 is essential for proper chromosome segregation

Kyung Uk Hong, Eunhee Kim, Chang-Dae Bae and Joobae Park
Pages 314 - 324
http://dx.doi.org/10.4161/cc.8.2.7597
Abstract | PDF

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), is a novel mitotic spindle-associated protein which is frequently up-regulated in various malignances. However, its cellular functions remain unknown. Previous reports suggested that the cellular functions of TMAP/CKAP2 pertain to regulation of the dynamics and assembly of the mitotic spindle. To investigate its role in mitosis, we studied the effects of siRNA-mediated depletion of TMAP/CKAP2 in cultured mammalian cells. Unexpectedly, TMAP/CKAP2 knockdown did not result in significant alterations of the spindle apparatus. However, TMAP/CKAP2-depleted cells often exhibited abnormal nuclear morphologies, which were accompanied by abnormal organization of the nuclear lamina, and chromatin bridge formation between two daughter cell nuclei. Time lapse video microscopy revealed that the changes in nuclear morphology and chromatin bridge formations observed in TMAP/CKAP2-depleted cells are the result of defects in chromosome segregation. Consistent with this, the spindle checkpoint activity was significantly reduced in TMAP/CKAP2-depleted cells. Moreover, chromosome missegregation induced by depletion of TMAP/CKAP2 ultimately resulted in reduced cell viability and increased chromosomal instability. Our present findings demonstrate that TMAP/CKAP2 is essential for proper chromosome segregation and for maintaining genomic stability.




LETTERS TO THE EDITOR

Open Access Article

Reduction of caldesmon expression induces apoptosis and causes disassembly of the sarcomeric protein complex in cardiomyocytes in vivo

Ping-Pin Zheng, Lies-Anne Severijnen, Rob Willemsen and Johan M. Kros
Pages 325 - 326
http://dx.doi.org/10.4161/cc.8.2.7344
PDF

Open Access Article

Polo-like kinase 4 phosphorylates Chk2

Steve Petrinac, Melissa L. Ganuelas, Sepal Bonni, Jordan Nantais and John W. Hudson
Pages 327 - 329
http://dx.doi.org/10.4161/cc.8.2.7355
PDF