FROM OUR SPECIAL CORRESPONDENT, FROM OUR WEATHER CORRESPONDENT, From Our Special Correspondent, FROM OUR CORRESPONDENT, FROM OUR NAVAL CORRESPONDENT, Our Political Correspondent, FROM OUR POLITICAL CORRESPONDENT, From Our Political Correspondent, FROM OUR MILITARY CORRESPONDENT, FROM A CORRESPONDENT, FROM OUR FILM CRITIC, FROM OUR ATHENS CORRESPONDENT, From Our Correspondent, FROM OUR OWN CORRESPONDENT, From Our Own Correspondent, FROM OUR DIPLOMATIC CORRESPONDENT, EDWARD HYAMS., DORIS LANGLEY MOORE., W. P. BANNISTER, PETER GORB., J. H. WESTERGAARD., JEAN GRAHAM HALL, R. J. L. KINGSFORD, J. SHEFFIELD., By Margery Perham, ANDREW ELPHINSTONE., JOHN A. TUTTON., WILLIAM ARNOLD., LESLIE BADHAM, FROM OUR UNIVERSITY CORRESPONDENT, FROM A CORRESPONDENT IN NEW YORK, FROM OUR CRICKET CORRESPONDENT, From Our Schools Cricket Correspondent, FROM OUR MOTOR RACING CORRESPONDENT, FROM OUR TENNIS CORRESPONDENT, From Our Racing Correspondent, FROM OUR NORTHERN CORRESPONDENT, From Our Rowing Correspondent, FROM OUR RIFLE SHOOTING CORRESPONDENT, FROM OUR POLO CORRESPONDENT, From Our Athletics Correspondent, FROM OUR YACHTING CORRESPONDENT, From Our Lawn Tennis Correspondent, From Our Golf Correspondent, By Our City Editor, J. V. D-H., R.G., A Correspondent, H. M. R., From Our Labour Correspondent, From Our Agricultural Correspondent, By a City Correspondent,
... Murder as a Cinematic Joke, Boisterous Baroque at Melk Age That Revelled in the Glory of Living, ...
1960 - Gale Group | TDA
Lionel Hebbard, Jochen Maurer, Amber Miller, Jacqueline Lesperance, John A. Hassell, Robert G. Oshima, Alexey V. Terskikh,
Abstract Maternal embryonic leucine zipper kinase (MELK) is expressed in several developing tissues, in the adult germ line, and in adult neural progenitors. MELK expression is elevated in aggressive undifferentiated tumors, correlating ... human breast cancer. To investigate the role of MELK in mammary tumorigenesis in vivo, we used a MELK-green fluorescent protein (GFP) reporter mouse, which allows prospective isolation of MELK-expressing cells based on GFP fluorescence. We found ... normal mammary gland, cells expressing high levels of MELK were enriched in proliferating cells that express markers ...
Tópico(s): Circular RNAs in diseases
2010 - American Association for Cancer Research | Cancer Research
Meng-Lay Lin, Jae‐Hyun Park, Toshihiko Nishidate, Yusuke Nakamura, Toyomasa Katagiri,
... cancers, we found maternal embryonic leucine-zipper kinase ( MELK ) to be significantly overexpressed in the great majority of breast cancer cells. To assess whether MELK has a role in mammary carcinogenesis, we knocked down the expression of endogenous MELK in breast cancer cell lines using mammalian vector- ... Bcl-2 family, as a possible substrate for MELK by pull-down assay with recombinant wild-type and kinase-dead MELK. Finally, we performed TUNEL assays and FACS analysis, measuring proportions of apoptotic cells, to investigate whether MELK is involved in the apoptosis cascade through the ...
Tópico(s): Circular RNAs in diseases
2007 - BioMed Central | Breast Cancer Research
Ichiro Nakano, Michael Masterman‐Smith, Kuniyasu Saigusa, Andres A. Paucar, Steve Horvath, Lorelei D. Shoemaker, Momoko Watanabe, Alejandra Negro, Ruchi Bajpai, Amy L. Howes, Vincent Lelièvre, James A. Waschek, Jorge A. Lazareff, William A. Freije, Linda M. Liau, Richard J. Gilbertson, Timothy F. Cloughesy, Daniel H. Geschwind, Stanley F. Nelson, Paul S. Mischel, Alexey V. Terskikh, Harley I. Kornblum,
... we demonstrated that maternal embryonic leucine zipper kinase (Melk) is highly expressed in murine neural stem cells and regulates their proliferation. Here we describe how MELK expression is correlated with pathologic grade of brain ... in younger glioblastoma patients. In normal human astrocytes, MELK is only faintly expressed, and MELK knockdown does not significantly influence their growth, whereas Ras and Akt overexpressing astrocytes have up‐regulated MELK expression, and the effect of MELK knockdown is ...
Tópico(s): Circular RNAs in diseases
2007 - Wiley | Journal of Neuroscience Research
Rika Saito, Hiromitsu Nakauchi, Sumiko Watanabe,
Serine/threonine kinase, Melk, was initially cloned in oocytes, but it is expressed in normal tissues and especially in cancer cells. We had previously identified Melk as a gene that is highly expressed in ... mouse retinal progenitors. To analyze the function of Melk in embryogenesis, we cloned zebrafish Melk and reported that morpholino-based downregulation of Melk in zebrafish resulted in severe anemia. Melk-morpholino-treated zebrafish also showed microphthalmia, suggesting the participation of Melk in retinal development. In Melk-depleted retinas, differentiation ...
Tópico(s): CRISPR and Genetic Engineering
2011 - Wiley | Cancer Science
B. Sis, Adis Tasanarong, Farhad Khoshjou, Farahnaz Dadras, Kim Solez, Philip F. Halloran,
... development of renal insufficiency in renal transplants.1.Melk A. Schmidt B.M. Vongwiwatana A. et al. ... the principal histological features of renal senescence.4.Melk A. Schmidt B.M. Takeuchi O. et al. ... in mammalian cells, known as extrinsic senescence.5.Melk A. Senescence of renal cells: molecular basis and ... diseases, such as hypertension and heart failure.5.Melk A. Senescence of renal cells: molecular basis and ... 2474-2478Crossref PubMed Scopus (74) Google Scholar,10.Melk A. Halloran P.F. Cell senescence and its ...
Tópico(s): Genetic and Kidney Cyst Diseases
2006 - Elsevier BV | Kidney International
Monique Beullens, Sadia Vancauwenbergh, Nick Morrice, Rita Derua, Hugo Ceulemans, Etienne Waelkens, Mathieu Bollen,
Maternal embryonic leucine zipper kinase (MELK) is a protein Ser/Thr kinase that has been implicated in stem cell renewal, cell cycle progression, and pre-mRNA splicing, ... are not yet known. We show here that MELK has a rather broad substrate specificity and does ... and Ser171 is required for the activation of MELK. The expression of MELK activity also requires reducing agents such as dithiothreitol or reduced glutathione. Furthermore, we show that MELK is a Ca2+-binding protein and is inhibited by physiological Ca2+ concentrations. The smallest MELK fragment that was still catalytically active comprises the ...
Tópico(s): Pancreatic function and diabetes
2005 - Elsevier BV | Journal of Biological Chemistry
Lieve Verlinden, Guy Eelen, Ine Beullens, Mark Van Camp, Paul Van Hummelen, Kristof Engelen, Ruth Van Hellemont, Kathleen Marchal, Bart De Moor, Floris Foijer, Hein te Riele, Monique Beullens, Mathieu Bollen, Chantal Mathieu, Roger Bouillon, Annemieke Verstuyf,
... 1 (Cnap1) and maternal embryonic leucine zipper kinase (Melk). Transfection studies and site-directed mutagenesis confirmed Cnap1 and Melk to be bona fide E2F targets. Repression of Cnap1 and Melk by 1,25(OH)2D3 was confirmed not ... 1 (Cnap1) and maternal embryonic leucine zipper kinase (Melk). Transfection studies and site-directed mutagenesis confirmed Cnap1 and Melk to be bona fide E2F targets. Repression of Cnap1 and Melk by 1,25(OH)2D3 was confirmed not ... genes were selected for further analysis, namely Cnap1, Melk, retroviral integration site 2 (Ris2), and enhancer of ...
Tópico(s): Vitamin D Research Studies
2005 - Elsevier BV | Journal of Biological Chemistry
Veerle Vulsteke, Monique Beullens, An Boudrez, Stefaan Keppens, Aleyde Van Eynde, Mark H. Rider, Willy Stalmans, Mathieu Bollen,
... the cell cycle-regulated protein Ser/Thr kinase MELK (maternal embryonic leucine zipper kinase). The NIPP1-MELK interaction was critically dependent on the phosphorylaton of Thr-478 of MELK and was increased in lysates from mitotically arrested cells. Recombinant MELK was a potent inhibitor of an early step ... mutation (T478A) of the NIPP1 binding site of MELK, indicating a mediatory role for NIPP1. Our data suggest that MELK has a role in the cell cycle-regulated ... the cell cycle-regulated protein Ser/Thr kinase MELK (maternal embryonic leucine zipper kinase). The NIPP1-MELK ...
Tópico(s): RNA modifications and cancer
2004 - Elsevier BV | Journal of Biological Chemistry
Tao Du, Ying Qu, Jianfang Li, Hao Li, Liping Su, Quan Zhou, Min Yan, Chen Li, Zhenggang Zhu, Bingya Liu,
Elevated MELK expression is featured in multiple tumors and correlated with tumorigenesis and tumor development. This study is aimed to investigate the mechanisms of MELK-mediated development of gastric cancer. MELK expression levels in human gastric cancer were determined by quantitative-PCR and immunohistochemistry. The effect of MELK on cell activity was explored by knockdown and ... To explore the molecular mechanism and effect of MELK on migration and invasion, Western blotting was used ... performed by tumor cell engraftment into nude mice. MELK mRNA and protein expression were both elevated in ...
Tópico(s): Cancer Mechanisms and Therapy
2014 - BioMed Central | Molecular Cancer
Houda Alachkar, Martin Mutonga, Klaus H. Metzeler, Noreen Fulton, Gregory Malnassy, Tobias Herold, Karsten Spiekermann, Stefan K. Bohlander, Wolfgang Hiddemann, Yo Matsuo, Wendy Stock, Yusuke Nakamura,
... Inc., Kanagawa, Japan Correspondence: Yusuke Nakamura, email: // Keywords : MELK, AML, OTS167 Received : September 17, 2014 Accepted : October ... 28, 2014 Abstract Maternal embryonic leucine-zipper kinase (MELK), which was reported to be frequently up-regulated ... Here we report characterization of possible roles of MELK in acute myeloid leukemia (AML). MELK is expressed in AML cell lines and AML blasts with higher levels in less differentiated cells. MELK is frequently upregulated in AML with complex karyotypes ...
Tópico(s): Pancreatic function and diabetes
2014 - Impact Journals LLC | Oncotarget
Chunyu Gu, Yeshavanth Banasavadi‐Siddegowda, Kaushal Joshi, Yuko Nakamura, Habibe Kurt, Snehalata Gupta, Ichiro Nakano,
... serine/threonine kinase maternal embryonic leucine-zipper kinase (MELK) is abundantly expressed in various cancers, the function and mechanism of MELK remain elusive. Here, we demonstrate that MELK depletion by shRNA diminishes the growth of GSC- ... 91 HGG tumors demonstrates that the proportion of MELK (+) cells is a statistically significant indicator of postsurgical survival periods. Mechanistically, MELK is regulated by the c-Jun NH(2)- ... JUN in GSCs but not in normal progenitors. MELK silencing induces p53 expression, whereas p53 inhibition induces ...
Tópico(s): Neurogenesis and neuroplasticity mechanisms
2013 - Oxford University Press | Stem Cells
Li Shen, Ziyu Li, Ting Guo, Xiaofang Xing, Xiaojing Cheng, Hong Du, Xianzi Wen, Jiafu Ji,
... Fu Ji, e-mail: jiafuj@hotmail.com Keywords: MELK, gastric cancer, prognosis, metastasis, PDX Received: July 02, ... 19, 2015 ABSTRACT Maternal embryonic leucine zipper kinase (MELK) is upregulated in a variety of human tumors, ... for cancer treatment. We characterized the expression of MELK in gastric cancer (GC) and measured the effects of reducing MELK mRNA levels and protein activity on GC growth. MELK was frequently overexpressed in primary GCs, and higher MELK levels correlated with worse clinical outcomes. Reducing MELK ...
Tópico(s): Cancer Mechanisms and Therapy
2015 - Impact Journals LLC | Oncotarget
Lijs Beke, Cenk Kığ, Joannes T. M. Linders, Shannah Boens, An Boeckx, Erika van Heerde, Marc Paradé, An De Bondt, Ilse Van den Wyngaert, Tarig Bashir, Souichi Ogata, Lieven Meerpoel, Aleyde Van Eynde, Christopher N. Johnson, Monique Beullens, Dirk Brehmer, Mathieu Bollen,
Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and is overexpressed in many cancer cells. The oncogenic function of MELK is attributed to its capacity to disable critical ... study, we have explored the biological function of MELK using MELK-T1, a novel and selective small-molecule inhibitor. Strikingly, MELK-T1 triggered a rapid and proteasome-dependent degradation of the MELK protein. Treatment of MCF-7 (Michigan Cancer Foundation-7) breast adenocarcinoma cells with MELK-T1 induced the accumulation of stalled replication forks ...
Tópico(s): PARP inhibition in cancer therapy
2015 - Portland Press | Bioscience Reports
Kiyokazu Hiwatashi, Shinichi Ueno, Masahiko Sakoda, Satoshi Iino, Koji Minami, Keiichi Yonemori, Yuka Nishizono, Hiroshi Kurahara, Yuko Mataki, Kosei Maemura, Hiroyuki Shinchi, Shoji Natsugoe,
Background/Aim: Maternal embryonic leucine zipper kinase (MELK) is categorized as a member of AMP-activated protein kinase families. Various MELK-associated cellular and biological processes affect multiple stages of tumorigenesis. ... present study was to clarify the relationship between MELK expression and hepatocellular carcinoma (HCC) clinicopathological features. Materials ... conserved frozen primary HCC and non-HCC samples MELK mRNA expression was examined by quantitative real-time ... higher expression levels compared to non-cancerous tissues. MELK expression had a statistically parallel correlation between tumor ...
Tópico(s): GDF15 and Related Biomarkers
2016 - International Institute of Anticancer Research (IIAR) Conferences 1997. Athens, Greece. Abstracts | Anticancer Research
Corey Speers, Shuang G. Zhao, Vishal Kothari, Alyssa Santola, Meilan Liu, Kari Wilder-Romans, Joseph R. Evans, Nidhi Batra, Harry Bartelink, Daniel F. Hayes, Theodore S. Lawrence, Powel H. Brown, Lori J. Pierce, Felix Y. Feng,
... PCR, and Western blotting were used to assess MELK RNA and protein expression levels. Clonogenic survival assays ... radiosensitivity of cell lines at baseline and after MELK inhibition. The effect of MELK knockdown on DNA damage repair kinetics was determined using γH2AX staining. The in vivo effect of MELK knockdown on radiosensitivity was performed using mouse xenograft ... identify potential factors impacting local recurrence-free survival.MELK expression is significantly elevated in breast cancer tissues ...
Tópico(s): Mechanisms of cancer metastasis
2016 - American Association for Cancer Research | Clinical Cancer Research
Andrew Stefka, Jin‐hong Park, Yo Matsuo, Sophie H. Chung, Yusuke Nakamura, Andrzej Jakubowiak, Shaun Rosebeck,
... uncertain. 2Expression of maternal embryonic leucine zipper kinase (MELK) is increased in a number of cancers and is associated with poorer prognosis.MELK activity modulates many cellular and biological processes, including ... stem cell maintenance. 3e assessed the expression of MELK mRNA in malignant PC derived from MM patients ... myeloma cell lines (HMCL) and effects of the MELK inhibitor OTS167 on myeloma cells, including drug-resistant ... mononuclear cells (PBMC) from patients with frank MM.MELK gene expression analysis was performed on publically available ...
Tópico(s): Peptidase Inhibition and Analysis
2016 - Springer Nature | Blood Cancer Journal
Shaohan Wu, Xujian Chen, Chundong Hu, Jing Wang, Yiyu Shen, Zhengxiang Zhong,
BACKGROUND Maternal embryonic leucine zipper kinase (MELK) has been implicated in various types of tumors, but its expression profile and clinicopathologic significance in hepatocellular carcinoma (HCC) in Chinese Han ... study attempted to investigate the expression pattern of MELK in HCC tissues obtained from a Chinese Han population. MATERIAL AND METHODS The expression of MELK, from RNA to protein levels, in HCC or ... that HCC tissues expressed a higher level of MELK RNA than non-tumor tissues in tumor-related ...
Tópico(s): Hormonal Regulation and Hypertension
2017 - International Scientific Information Inc. | Medical Science Monitor
Radoslav Janoštiak, Navin Rauniyar, TuKiet T. Lam, Jianhong Ou, Lihua Julie Zhu, Michael R. Green, Narendra Wajapeyee,
Highlights•MELK is upregulated in melanoma by the MAPK pathway via E2F1•MELK inhibition blocks melanoma growth•MELK phosphorylates a large number of BRAF and MEK substrates•MELK partly promotes melanoma by stimulating the NF-κB ... melanoma cells that maternal embryonic leucine zipper kinase (MELK) is transcriptionally upregulated by the MAPK pathway via transcription factor E2F1. MELK knockdown or pharmacological inhibition blocked melanoma growth and ... inhibitor against melanoma cells. To identify mediators of MELK function, we performed stable isotope labeling with amino ...
Tópico(s): RNA regulation and disease
2017 - Cell Press | Cell Reports
Christopher J. Giuliano, Ann Lin, Joan C. Smith, Ann Palladino, Jason M. Sheltzer,
The Maternal Embryonic Leucine Zipper Kinase (MELK) has been identified as a promising therapeutic target in multiple cancer types. MELK over-expression is associated with aggressive disease, and MELK has been implicated in numerous cancer-related processes, ... lines harboring CRISPR/Cas9-induced null mutations in MELK proliferate at wild-type levels in vitro (<xref ... Here, we generate several additional knockout clones of MELK and demonstrate that across cancer types, cells lacking MELK exhibit wild-type growth in vitro, under environmental ...
Tópico(s): MicroRNA in disease regulation
2018 - eLife Sciences Publications Ltd | eLife
Katja Kiseljak‐Vassiliades, Yu Zhang, Adwitiya Kar, Raud Razzaghi, Mei Xu, Katherine Gowan, Christopher D. Raeburn, Maria Albuja‐Cruz, Kenneth L. Jones, Hilary Somerset, Lauren Fishbein, Stephen Leong, Margaret E. Wierman,
... analyses, we identified maternal embryonic leucine zipper kinase (MELK) as 4.1-fold overexpressed in ACC compared with normal adrenal samples. High MELK expression in human tumors correlated with shorter survival ... and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells. In vitro treatment with the MELK inhibitor, OTSSP167, resulted in a dose-dependent decrease ... ACC cell line based upon the level of MELK overexpression. To confirm a MELK-specific antitumorigenic effect, ...
Tópico(s): Adrenal and Paraganglionic Tumors
2018 - Oxford University Press | Endocrinology
Juan Wang, Yamei Wang, Fangrong Shen, Yanting Xu, Yinghui Zhang, Xinwei Zou, Jinhua Zhou, Youguo Chen,
Maternal embryo leucine zipper kinase (MELK) is highly expressed in a variety of malignant tumors and involved in cell cycle regulation, cell proliferation, apoptosis, tumor formation etc However, the biological effects of MELK in cervical cancer are still uninvestigated. This study aimed to explore the expression of MELK in cervical cancer, as well as its effects ... techniques were used to detect the expression of MELK in cervical cancer tissues, paracancerous tissues, and cervical ... Several cervical cancer cell lines were treated with MELK knockdown by siRNA and MELK selective inhibitor OTSSP167. ...
Tópico(s): Cancer-related molecular mechanisms research
2018 - Wiley | Cancer Medicine
Xianling Gong, Zhihong Chen, Qinrui Han, Chunhui Chen, Linlin Jing, Yawei Liu, Liang Zhao, Xueqing Yao, Xuegang Sun,
... staining, respectively. The in vitro kinase activity of MELK was analyzed by using HTRF® KinEASE™-STK kit. ... used to study the interaction between STRAP and MELK. The anti-neoplastic effect of sanguinarine was observed ... protein (STRAP) and maternal embryonic leucine zipper kinase (MELK) were observed in Bax positive cells but not in Bax negative cells. Sanguinarine dephosphorylated STRAP and MELK and disrupted the association between them in HCT116 ... cells. The expression and association between STRAP and MELK were also attenuated by sanguinarine in the tumor ...
Tópico(s): FOXO transcription factor regulation
2018 - BioMed Central | BMC Cancer
Gang Li, Mei Yang, Li Zuo, Wang Meixing,
Maternal embryonic leucine zipper kinase (MELK) is an important regulator in tumorigenesis of human breast cancer, and if silenced leads to programmed cell death in specific breast ... proteins were performed to determine the effects of MELK in human breast cancer cells. Data demonstrated that the highest level of MELK protein in the MDA‑MB‑231 cell line ... eight breast cancer cell lines. The sensitivity of MELK small interfering‑RNA varied in different breast cancer cell lines, but MELK silencing resulted in marked suppression of proliferation of ...
Tópico(s): GDF15 and Related Biomarkers
2018 - Spandidos Publishing | Oncology Letters
Lili Ren, Boya Deng, Vassiliki Saloura, Jae‐Hyun Park, Yusuke Nakamura,
Maternal embryonic leucine zipper kinase (MELK) has been reported to serve critical roles in the maintenance of stemness of cancer cells, although its mechanism remains unclear. Since ... aberrantly expressed in HNSCC tumors, the association between MELK and SOX2 was examined. Firstly, MELK inhibition was performed by small interfering RNA or MELK inhibitor OTS167, and it was determined that MELK inhibition by these approaches could decrease the SOX2 ... dose‑dependent manner. The present results indicated that MELK inhibition may target cancer stem cells (CSCs) through ...
Tópico(s): Circular RNAs in diseases
2019 - Elsevier BV | Oncology Reports
Antonio Cigliano, Maria G. Pilo, Marta Mela, Silvia Ribback, Frank Dombrowski, Giovanni Mario Pes, Antonio Cossu, Matthias Evert, Diego F. Calvisi, Kirsten Utpatel,
... role of the maternal embryonic leucine zipper kinase (MELK) protooncogene in iCCA. Materials and Methods: We analyzed the expression of MELK and two putative targets, Forkhead Box M1 (FOXM1) ... OTSSP167 and specific small-interfering RNA (siRNA) against MELK were investigated in iCCA cell lines. Results: Expression of MELK was significantly higher in tumors than in corresponding non-neoplastic liver counterparts, with highest levels of MELK being associated with patients’ shorter survival length. In ... Similar results, but less remarkable, were obtained when MELK was silenced by specific siRNA in the same ...
Tópico(s): FOXO transcription factor regulation
2019 - Multidisciplinary Digital Publishing Institute | Medicina
Alexandre Chlenski, Chanyoung Park, Marija Dobratic, Helen R. Salwen, Brian Budke, Jae-Hyun Park, R J Miller, Mark A. Applebaum, Emma Wilkinson, Yusuke Nakamura, Philip P. Connell, Susan L. Cohn,
Abstract Maternal embryonic leucine zipper kinase (MELK) activates pathways that mediate aggressive tumor growth and therapy resistance in many types of adult cancers. Pharmacologic and genomic inhibition of MELK impairs tumor growth and increases sensitivity to radiation ... studies, early-phase adult clinical trials testing the MELK inhibitor OTS167 are ongoing. To investigate whether MELK is also a therapeutic target in neuroblastoma, we analyzed MELK expression in primary tumors and cell lines, and ...
Tópico(s): Signaling Pathways in Disease
2019 - American Association for Cancer Research | Molecular Cancer Therapeutics
Ian M. McDonald, Lee M. Graves,
The Ser/Thr protein kinase MELK (maternal embryonic leucine zipper kinase) has been considered an attractive therapeutic target for managing cancer since 2005. Studies using expression analysis have indicated that MELK expression is higher in numerous cancer cells and ... in their normal, nonneoplastic counterparts. Further, RNAi-mediated MELK depletion impairs proliferation of multiple cancers, including triple- ... growth defects can be rescued with exogenous WT MELK, but not kinase-dead MELK complementation. Pharmacological MELK ...
Tópico(s): CRISPR and Genetic Engineering
2020 - Elsevier BV | Journal of Biological Chemistry
Ian M. McDonald, Gavin D. Grant, Michael P. East, Thomas S.K. Gilbert, Emily Wilkerson, Dennis Goldfarb, Joshua Beri, Laura E. Herring, Cyrus Vaziri, Jeanette Gowen Cook, Michael J. Emanuele, Lee M. Graves,
The maternal embryonic leucine zipper kinase (MELK) has been implicated in the regulation of cancer cell proliferation. RNAi-mediated MELK depletion impairs growth and causes G2/M arrest in ... underlying these effects are poorly understood. Furthermore, the MELK inhibitor OTSSP167 has recently been shown to have poor selectivity for MELK, complicating the use of this inhibitor as a tool compound to investigate MELK function. Here, using a cell-based proteomics technique ... MS), we profiled the selectivity of two additional MELK inhibitors, NVS-MELK8a (8a) and HTH-01-091. ...
Tópico(s): Metabolism, Diabetes, and Cancer
2020 - Elsevier BV | Journal of Biological Chemistry
Lakshmi Reddy Bollu, Jonathan H. Shepherd, Dekuang Zhao, Yanxia Ma, William M. Tahaney, Corey Speers, Abhijit Mazumdar, Gordon B. Mills, Powel H. Brown,
... Previously, we identified maternal embryonic leucine zipper kinase (MELK) to be highly expressed in TNBCs as compared ... Here we determined the molecular mechanism by which MELK is overexpressed in TNBCs. Analysis of publicly available data sets revealed that MELK mRNA is elevated in p53-mutant breast cancers. Consistent with this observation, MELK protein levels are higher in p53-mutant vs. ... loss or mutation of the p53 gene, increases MELK expression, whereas overexpression of wild-type p53 in p53-null cells reduces MELK promoter activity and MELK expression. We further analyzed ...
Tópico(s): Genomics, phytochemicals, and oxidative stress
2020 - Nature Portfolio | npj Breast Cancer