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Maeva Dufies, Damien Ambrosetti, Sonia Boulakirba, Anne Calleja, Coline Savy, Nathan Furstoss, Marwa Zerhouni, Julien Parola, Lazaro Aira-Diaz, Sandrine Marchetti, Francois Orange, Sandra Lacas-Gervais, Frederic Luciano, Arnaud Jacquel, Guillaume Robert, Gilles Pagès, Patrick Auberger
Polo-like kinases (Plks) define a highly conserved family of Ser/Thr kinases with crucial roles in the regulation of cell division. Here we show that Plk1 is cleaved by caspase 3, but not by other caspases in different hematopoietic cell lines treated with competitive inhibitors of the ATP-binding pocket of Plk1. Intriguingly, Plk1 was not cleaved in cells treated with Rigosertib, a non-competitive inhibitor of Plk1, suggesting that binding of the inhibitor to the ATP binding pocket of Plk1 triggers a conformational change and unmasks a cryptic caspase 3 cleavage site on the protein...
February 16, 2018: Oncotarget
Ernesto R Bongarzone, Mary C McKenna, Araceli Espinosa-Jeffrey, Nancy Wainwright, Cristina Ghiani, J Regino Perez-Polo, Arne Schousboe, Eric M Prager
No abstract text is available yet for this article.
May 2018: Journal of Neuroscience Research
Jianwen Dong, Soon Young Park, Nghi Nguyen, Ravesanker Ezhilarasan, Emmanuel Martinez-Ledesma, Shaofang Wu, Verlene Henry, Yuji Piao, Ningyi Tiao, David Brunell, Clifford Stephan, Roel Verhaak, Erik Sulman, Veerakumar Balasubramaniyan, John F de Groot
Background: Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM). Results: The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR)...
February 13, 2018: Oncotarget
Tea Galic, Domagoj Kuncic, Tina Poklepovic Pericic, Ivan Galic, Frane Mihanovic, Josko Bozic, Mark Herceg
BACKGROUND/AIMS: The increasing popularity of participating in sports activities among children and adolescents has increased the risk of sports-retaled orofacial and dental injuries. Therefore, it is important to establish efficient preventive strategies regarding sports-related dental trauma The aim of this study was to evaluate the occurrence of sports-related dental injuries in young athletes and to compare the frequency of such injuries between high-risk and medium-risk sports, along with assessing athletes' attitudes and habits regarding mouthguard use...
March 11, 2018: Dental Traumatology: Official Publication of International Association for Dental Traumatology
Jaana Seikkula, Sanna Oksjoki, Saija Hurme, Harri Mankonen, Päivi Polo-Kantola, Varpu Jokimaa
Blastomere multinucleation in human embryos is a common phenomenon, but data on its effect on pregnancy outcome and the health of newborns are scarce. In this case-control study, we assessed pregnancy and perinatal outcomes from 136 binucleated and multinucleated frozen-thawed embryo transfer cycles against a control group of 136 non-binucleated and multinucleated frozen embryo transfer cycles. Clinical pregnancy and live birth rates were lower among the case group (29.4% versus 44.1%, P = 0.012; 22.1% versus 36...
February 26, 2018: Reproductive Biomedicine Online
Simon Gemble, Renata Basto
In each duplication cycle, daughter centrioles grow to the same length as their mothers. Which mechanisms regulate this fidelity to maintain centriole length is not known. In this issue, Aydogan et al. (2018. J. Cell Biol. report a novel role for Polo-like kinase 4 (Plk4). They found that Plk4 functions in a homeostatic manner to balance growth rate and growth period to set the final centriole size.
March 8, 2018: Journal of Cell Biology
Bhavani Gopalakrishnan, Carolyn Cheney, Rajeswaran Mani, Xiaokui Mo, Donna Bucci, Alison Walker, Rebecca Klisovic, Bhavana Bhatnagar, Katherine Walsh, Bjoern Rueter, Irene C Waizenegger, Karl-Heinz Heider, William Blum, Sumithira Vasu, Natarajan Muthusamy
Acute myeloid leukemia (AML) is the second most common type of leukemia in adults. Incidence of AML increases with age with a peak incidence at 67 years. Patients older than 60 years have an unfavorable prognosis due to resistance to conventional chemotherapy. Volasertib (BI 6727) is a cell-cycle regulator targeting polo-like kinase which has been evaluated in clinical trials in AML. We evaluated effects of volasertib in primary patient samples and NK cells. At equivalent doses, volasertib is cytotoxic to AML blasts but largely spares healthy NK cells...
February 9, 2018: Oncotarget
M Gianneli, E Polo, H Lopez, V Castagnola, T Aastrup, K A Dawson
Nanomedicine, nanotargeting and nanotherapeutics have in the last few years faced several difficulties in translating the promising results obtained in vitro to an in vivo scenario. The origin of this discrepancy might be found in the lack of a detailed and realistic characterization of the biological surface of nanoparticles. Despite the capability to engineer nanomaterials with a great variety and a precise control of the surface functionalization, the targeting capability is lost when the nanoparticles are embedded in complex biological media, due to the formation of a biological layer (biomolecular corona)...
March 7, 2018: Nanoscale
Riina Katainen, Janne R Engblom, Päivi Polo-Kantola
OBJECTIVE: Only a few extended follow-up studies have investigated the natural progress of climacteric-related symptoms. The results have been conflicting. Thus, our aim was to evaluate, through a 19-year longitudinal study, whether these symptoms decrease or disappear as time elapses after menopause. METHODS: Our study was a prospective follow-up survey of 65 hysterectomized peri or postmenopausal women. The women were interviewed at the baseline, and at 6 and 19 years thereafter...
March 5, 2018: Menopause: the Journal of the North American Menopause Society
Javier Brugos, Javier A Cabeza, Pablo García-Álvarez, Enrique Pérez-Carreño, Diego Polo
The non-donor-stabilized PSnP pincer-type stannylene Sn(NCH2 Pt Bu2 )2 C6 H4 (1) has been prepared by treating SnCl2 with Li2 (NCH2 Pt Bu2 )2 C6 H4 . All attempts to synthesize the analogous PSiP silylene by reduction of the (previously unknown) silanes SiCl2 (NCH2 Pt Bu2 )2 C6 H4 (2), SiHCl(NCH2 Pt Bu2 )2 C6 H4 (3) and SiH(HMDS)(NCH2 Pt Bu2 )2 C6 H4 (4; HMDS = N(SiMe3 )2 ) have been unsuccessful. The almost planar (excluding the tert-butyl groups) molecular structure of stannylene 1 (determined by X-ray crystallography) has been rationalized with the help of DFT calculations, which have shown that, in the series of diphosphanetetrylenes E(NCH2 Pt Bu2 )2 C6 H4 (E = C, Si, Ge, Sn), the most stable conformation of the compounds with E = Ge and Sn has both P atoms very close to the EN2 C6 H4 plane, near (interacting with) the E atom, whereas for the compounds with E = C and Si, both phosphane groups are located at one side of the EN2 C6 H4 plane and far away from the E atom...
March 6, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Ayaka Okamoto, Tomohiro Asai, Yusuke Hirai, Kosuke Shimizu, Hiroyuki Koide, Tetsuo Minamino, Naoto Oku
Triple-negative breast cancer is one of intractable cancers that are not sensitive to the treatment with existing molecular-targeted drugs. Recently, there has been much interest in RNA interference-mediated treatment of triple-negative breast cancer. In the present study, we have developed lipid nanoparticles encapsulating siRNA (LNP-siRNA) decorated with an Fab' antibody against heparin-binding EGF-like growth factor (αHB-EGF LNP-siRNA). αHB-EGF LNP-siRNA targeting polo-like kinase 1 (PLK1) was prepared and evaluated for its anticancer effect using MDA-MB-231 human triple-negative breast cancer cells overexpressing HB-EGF on their cell surface...
March 5, 2018: Molecular Pharmaceutics
Mustafa G Aydogan, Alan Wainman, Saroj Saurya, Thomas L Steinacker, Anna Caballe, Zsofia A Novak, Janina Baumbach, Nadine Muschalik, Jordan W Raff
Centrioles are highly structured organelles whose size is remarkably consistent within any given cell type. New centrioles are born when Polo-like kinase 4 (Plk4) recruits Ana2/STIL and Sas-6 to the side of an existing "mother" centriole. These two proteins then assemble into a cartwheel, which grows outwards to form the structural core of a new daughter. Here, we show that in early Drosophila melanogaster embryos, daughter centrioles grow at a linear rate during early S-phase and abruptly stop growing when they reach their correct size in mid- to late S-phase...
March 2, 2018: Journal of Cell Biology
Patricia Gómez-Suaga, José M Bravo-San Pedro, Rosa A González-Polo, José M Fuentes, Mireia Niso-Santano
Mitochondria form close physical contacts with a specialized domain of the endoplasmic reticulum (ER), known as the mitochondria-associated membrane (MAM). This association constitutes a key signaling hub to regulate several fundamental cellular processes. Alterations in ER-mitochondria signaling have pleiotropic effects on a variety of intracellular events resulting in mitochondrial damage, Ca2+ dyshomeostasis, ER stress and defects in lipid metabolism and autophagy. Intriguingly, many of these cellular processes are perturbed in neurodegenerative diseases...
March 1, 2018: Cell Death & Disease
Tiffany A McLamarrah, Daniel W Buster, Brian J Galletta, Cody J Boese, John M Ryniawec, Natalie Ann Hollingsworth, Amy E Byrnes, Christopher W Brownlee, Kevin C Slep, Nasser M Rusan, Gregory C Rogers
Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 is then phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STil/ANa2 (STAN) domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site...
March 1, 2018: Journal of Cell Biology
Jordi Vilardell, Cristina Girardi, Oriano Marin, Giorgio Cozza, Lorenzo A Pinna, Maria Ruzzene
CK2 is a pleiotropic S/T protein kinase (formerly known as casein kinase 2) which is attracting increasing interest as therapeutic target, and the identification of its substrates is a crucial step in determining its involvement in different pathological conditions. We recently found that S131 of Akt2 (homologous to the well established CK2 target S129 of Akt1) is not phosphorylated by CK2 either in vitro or in vivo, although the consensus sequence recognized by CK2 (S/T-x-x-E/D/pS/pT) is conserved in it. Here, by exploiting synthetic peptides, in cell transfection experiments, and computational analysis, we show that a single sequence element, a T at position n+1, hampers phosphorylation, causing an α-helix structure organization which prevents the recognition of its own consensus by CK2...
2018: PloS One
Geun-Hyoung Ha, Dong-Young Kim, Eun-Kyoung Breuer, Chung Kwon Kim
BACKGROUND/AIM: Breast cancer is the most common malignant cancer type in women, and triple-negative breast cancer (TNBC) is an extremely aggressive subtype of breast cancer with poor prognosis rates. The present study investigated the antitumor effect of polo-like kinase 1 (PLK1) inhibitor in combination with the tankyrase-1 (TNKS1) inhibitor on TNBC cells. MATERIALS AND METHODS: We evaluated the antitumor effects of combination therapy with PLK1 and TNKS1 inhibitor using cell viability analysis, apoptosis assay and transwell assay for cell invasion and migration in TNBC cells...
March 2018: Anticancer Research
Ines J de Castro, Raquel Sales Gil, Lorena Ligammari, Maria Laura Di Giacinto, Paola Vagnarelli
Micronuclei (MN) arise from chromosomes or fragments that fail to be incorporated into the primary nucleus after cell division. These structures are a major source of genetic instability caused by DNA repair and replication defects coupled to aberrant Nuclear Envelope (NE). These problems ultimately lead to a spectrum of chromosome rearrangements called chromothripsis, a phenomenon that is a hallmark of several cancers. Despite its importance, the molecular mechanism at the origin of this instability is still not understood...
January 30, 2018: Oncotarget
Sabine A G Cuijpers, Alfred C O Vertegaal
Cell division is tightly regulated to disentangle copied chromosomes in an orderly manner and prevent loss of genome integrity. During mitosis, transcriptional activity is limited and post-translational modifications (PTMs) are responsible for functional protein regulation. Essential mitotic regulators, including polo-like kinase 1 (PLK1) and cyclin-dependent kinases (CDK), as well as the anaphase-promoting complex/cyclosome (APC/C), are members of the enzymatic machinery responsible for protein modification...
February 24, 2018: Trends in Biochemical Sciences
Ke Liu, Lijing Fang, Haiyan Sun, Zhengyin Pan, Jianchao Zhang, Juntao Chen, Ximing Shao, Wei Wang, Yuanyan Tan, Zhihao Ding, Lijiao Ao, Chunlei Wu, Xiaoqi Liu, Huashun Li, Rui Wang, Wu Su, Hongchang Li
The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide-Hoechst conjugate, PIP3, targeted to specific DNA sequence in the Plk1 promoter...
February 26, 2018: Molecular Cancer Therapeutics
Valthierre Nunes de Lima, Gustavo Antonio Correa Momesso, Luara Teixeira Colombo, Gabriel Mulinari-Santos, Cecília Alves de Sousa, Tárik Ocon Braga Polo, Idelmo Rangel Garcia-Júnior, Leonardo Perez Faverani
The frequency of accidents due to dog bite in children is high, and in the most cases, the child already knows the aggressor dog. Patient, 3 years, female, melanoderm, victim of pet dog attack on the right side of the face region. After the physical examination, conscious sedation was performed with the supplementation of oxygen by pediatrics and the suture by oral and maxillofacial surgeon, under local anesthesia with adrenergic vasoconstrictor, with internal points in the muscles using vicryl 4-0 and in the skin with 5-0 nylon; the lesser number of stitches were performed in the lower region of the wound, allowing spontaneous drainage spaces...
February 23, 2018: Journal of Craniofacial Surgery
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