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Polo-like kinase

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https://www.readbyqxmd.com/read/29652009/immunohistochemical-expression-of-polo-like-kinase-1-in-oral-squamous-cell-carcinoma-and-oral-submucous-fibrosis
#1
Kavitha Vittal, Sathasivasubramanian Sankara Pandian, Leena Dennis Joseph, Shilpa Germaine Raj
Context: Polo-like kinase 1 (PLK1) is a critical molecule in the proliferation of several human cancers. Overexpression of PLK1 has been correlated with cancer cell proliferation and lower overall survival rates. Although PLK1 has been studied in various tumors, information regarding its expression in oral cancer and precancer is limited. Aims: This study is aimed at evaluating the expression of PLK1 in a potentially malignant and malignant disorder of the oral cavity, namely, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC), respectively, using the immunohistochemistry technique...
March 2018: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
https://www.readbyqxmd.com/read/29649211/stable-centrosomal-roots-disentangle-to-allow-interphase-centriole-independence
#2
Robert Mahen
The centrosome is a non-membrane-bound cellular compartment consisting of 2 centrioles surrounded by a protein coat termed the pericentriolar material (PCM). Centrioles generally remain physically associated together (a phenomenon called centrosome cohesion), yet how this occurs in the absence of a bounding lipid membrane is unclear. One model posits that pericentriolar fibres formed from rootletin protein directly link centrioles, yet little is known about the structure, biophysical properties, or assembly kinetics of such fibres...
April 12, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29645088/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#3
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29608426/identification-of-hub-genes-and-pathways-in-zika-virus-infection-using-rna-seq-data-a-network-based-computational-approach
#4
Rahul Brahma, Sanathoi Gurumayum, Leimarembi Devi Naorem, Mathavan Muthaiyan, Jeyakodi Gopal, Amouda Venkatesan
Zika virus (ZIKV), a single-strand RNA flavivirus, is transmitted primarily through Aedes aegypti. The recent outbreaks in America and unexpected association between ZIKV infection and birth defects have triggered the global attention. This vouches to understand the molecular mechanisms of ZIKV infection to develop effective drug therapy. A systems-level understanding of biological process affected by ZIKV infection in fetal brain sample led us to identify the candidate genes for pharmaceutical intervention and potential biomarkers for diagnosis...
April 2, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29597073/p21-activated-kinase-1-nuclear-activity-and-its-role-during-dna-damage-repair
#5
REVIEW
Eloy Andrés Pérez-Yépez, Héctor Iván Saldívar-Cerón, Olga Villamar-Cruz, Carlos Pérez-Plasencia, Luis Enrique Arias-Romero
p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small GTPases Rac1 and Cdc42. It is located in the chromosome 11q13 and is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme plays a pivotal role in the control of a number of fundamental cellular processes by phosphorylating its downstream substrates. In addition to its role in the cytoplasm, it is well documented that PAK1 also plays crucial roles in the nucleus participating in mitotic events and gene expression through its association and/or phosphorylation of several transcription factors, transcriptional co-regulators and cell cycle-related proteins, including Aurora kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor (FKHR), estrogen receptor α (ERα), and Snail...
March 21, 2018: DNA Repair
https://www.readbyqxmd.com/read/29568868/polo-like-kinase-2-promotes-chemoresistance-and-predicts-limited-survival-benefit-from-adjuvant-chemotherapy-in-colorectal-cancer
#6
Yuquan Xie, Ying Liu, Qiubo Li, Jianming Chen
Colorectal cancer (CRC) is one of the most common malignances worldwide. Chemoresistance remains a major issue in the field of CRC treatment. The present study aimed to investigate the potential role of polo-like kinase 2 (Plk2) in chemoresistance in CRC. The associations between Plk2 and clinicopathological factors, as well as chemotherapeutic benefit were analyzed with a publicly available CRC dataset. The correlation between Plk2 expression and chemosensitivity was further confirmed in CRC cells. Moreover, knockdown and exogenous overexpression experiments of Plk2 were carried out to uncover the potential role of Plk2 in regulating the chemoresistance of CRC cells...
March 20, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29565459/plk1-interacts-with-rnf2-and-promotes-its-ubiquitin%C3%A2-dependent-degradation
#7
Ran An, Li Cheng, Lijian Chen, Jian Du
Ring finger protein 2 (RNF2), also known as RING2 or RING1B, displays oncogenic functions in different types of cancers, yet, the function of RNF2 during mitosis has not been evaluated. A yeast two‑hybrid screen was undertaken using a human HeLa cDNA library to explore and identify proteins that interact with RNF2. Several positive clones, including Polo‑like kinase 1 (Plk1), a critical regulator of mitosis, were identified. The interaction between RNF2 and Plk1 was confirmed using a β‑galactosidase and growth test in selective media, in vitro glutathione S‑transferase pull‑down, and in vivo immunoprecipitation assays...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29555478/inhibition-of-tacc3-by-a-small-molecule-inhibitor-in-breast-cancer
#8
Loredana Campo, Eun-Kyoung Breuer
Studies have shown that transforming acidic coiled-coil protein 3 (TACC3), a key component of centrosome-microtubule dynamic networks, is significantly associated with various types of human cancer. We have recently reported that high levels of TACC3 are found in breast cancer, lead to the accumulation of spontaneous DNA damage due to defective DNA damage response signaling, and confer cellular sensitivity to radiation and poly(ADP-ribose) polymerase (PARP) inhibitors. Although our study suggests a potential role of TACC3 as a biomarker in breast cancer detection and prediction of therapy outcome, its role as a therapeutic target in breast cancer is not well studied...
March 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29541386/atp-competitive-plk1-inhibitors-induce-caspase-3-mediated-plk1-cleavage-and-activation-in-hematopoietic-cell-lines
#9
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
https://www.readbyqxmd.com/read/29535822/the-polo-like-kinase-1-inhibitor-volasertib-synergistically-increases-radiation-efficacy-in-glioma-stem-cells
#10
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
https://www.readbyqxmd.com/read/29519803/fast-and-furious-or-not-plk4-dictates-the-pace
#11
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. https://doi.org/10.1083/jcb.201801014) 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
https://www.readbyqxmd.com/read/29515764/polo-like-kinase-inhibitor-volasertib-marginally-enhances-the-efficacy-of-the-novel-fc-engineered-anti-cd33-antibody-bi-836858-in-acute-myeloid-leukemia
#12
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
https://www.readbyqxmd.com/read/29502423/systemic-administration-of-sirna-with-anti-hb-egf-antibody-modified-lipid-nanoparticles-for-the-treatment-of-triple-negative-breast-cancer
#13
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
https://www.readbyqxmd.com/read/29500190/a-homeostatic-clock-sets-daughter-centriole-size-in-flies
#14
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
https://www.readbyqxmd.com/read/29496738/an-ordered-pattern-of-ana2-phosphorylation-by-plk4-is-required-for-centriole-assembly
#15
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
https://www.readbyqxmd.com/read/29494643/the-importance-of-negative-determinants-as-modulators-of-ck2-targeting-the-lesson-of-akt2-s131
#16
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
https://www.readbyqxmd.com/read/29491053/combination-treatment-of-polo-like-kinase-1-and-tankyrase-1-inhibitors-enhances-anticancer-effect-in-triple-negative-breast-cancer-cells
#17
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
https://www.readbyqxmd.com/read/29487689/cdk1-and-plk1-coordinate-the-disassembly-and-reassembly-of-the-nuclear-envelope-in-vertebrate-mitosis
#18
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
https://www.readbyqxmd.com/read/29486978/guiding-mitotic-progression-by-crosstalk-between-post-translational-modifications
#19
REVIEW
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
https://www.readbyqxmd.com/read/29483218/targeting-polo-like-kinase-1-by-a-novel-pyrrole-imidazole-polyamide-hoechst-conjugate-suppresses-tumor-growth-in-vivo
#20
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
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