MELK, also known as murine protein serine/threonine kinase 38 (MPK38) [ 1 ] and Eg3 protein (pEg3) [ 2 ], was originally identified as a signal transduction factor by Gil et al. Daniel Geschwind. 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 cancer cell lines, including MDA-MB-231 cells. MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE (HUMAN CLONE MGC:20350 IMAGE:4547136) PEG3 KINASE; PROTEIN KINASE EG3; PROTEIN KINASE PK38; TYROSINE-PROTEIN KINASE MELK; Resources. Pharmacologic and genomic inhibition of MELK impairs tumor growth and increases sensitivity to radiation and chemotherapy. Alexey Terskikh. 9 MELK is highly expressed in a wide range of malignant tumors, including hepatocellular 2004), cell division, and cytokine- Abstract. Maternal Embryonic Leucine Zipper Kinase (MELK): a Novel Marker of Poor Prognosis and Attractive Drug Target in High-Risk Patients with Multiple Myeloma Arnold Bolomsky, Arnold Bolomsky * 1 Department of Medicine I, Wilhelminenhospital, Wilhelminen Cancer Research Institute, Vienna, Austria . Maternal embryonic leucine zipper kinase (MELK), a member of the sucrose-non-fermenting (SNF1)/AMPK family of serine-threonine kinases, is a cell cycle dependent protein kinase [7,8]. MELK inhibitor related products. Gene names . MELK-8a also inhibits Flt3 (ITD), Haspin, PDGFRα with IC50s of 0.18, 0.19, and 0.42 μM, respectively. Maternal Embryonic Leucine Zipper Kinase (MELK): a Novel Marker of Poor Prognosis and Attractive Drug Target in High-Risk Patients with Multiple Myeloma Arnold Bolomsky, Arnold Bolomsky * 1 Department of Medicine I, Wilhelminenhospital, Wilhelminen Cancer Research Institute, Vienna, Austria . Initial studies that characterized HPK38; maternal embryonic leucine zipper kinase; pEg3 kinase; protein kinase Eg3; protein kinase PK38; tyrosine-protein kinase MELK Background. Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. A Biblioteca Virtual em Saúde é uma colecao de fontes de informacao científica e técnica em saúde organizada e armazenada em formato eletrônico nos países da Região Latino-Americana e do Caribe, acessíveis de forma universal na Internet de modo compatível com as bases internacionais. MELK was highly expressed in clinical specimens of cervical cancer patients and the . Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells. MELK Origin: Human Host: Wheat germ Recombinant AP, AA, ELISA, WB camera_alt 1 image . The present study aimed to explore the clinical significance of MELK in the . Maternal Embryonic Leucine Zipper Kinase (MELK) (AA 550-650) protein (GST tag) Protein. Introduction. Abstract. Search for other works by this author on: . Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Maternal embryo leucine zipper kinase is highly expressed in a wide range of cancer and is associated with the degree of malignancy of the tumor. MELK-8a (NVS-MELK8a) is a highly potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor with IC50 of 2 nM. OTSSP167, an orally administrated inhibitor . Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Ichiro Nakano. 2005), pre-mRNA pro-cessing (Vulsteke et al. MELK kinase has been implicated in playing an important role in tumorigenesis. MELK plays an important role in cell cycle regulation, cell proliferation and other processes [7,8,9]. Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Europe PMC is an archive of life sciences journal literature. Background Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in cell cycle, differentiation, proliferation, and apoptosis. Maternal embryonic leucine zipper kinase (EC: 2.7.11.1 ) Short name: MELK. Maternal embryonic leucine zipper kinase (Predicted) Imported However, to the best of our knowledge, the effect of MELK in lung adenocarcinoma (LUAD) has not been elucidated. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. James Waschek. Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. MELK plays a key role in tumor cell cycle regulation and growth signaling pathways ().Increased expression of MELK has been observed in TNBC tumor cells and tumor stem cells , , , , , which is associated with inhibition of tumor cell . From this approach, we have found that maternal embryonic leucine zipper kinase (Melk), a member of the AMP serine/threonine kinase family, exhibits multiple features . Amy Howes. Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. MELK (maternal embryonic leucine zipper kinase), which is a member of the AMPK (AMP-activated protein kinase)-related kinase family, plays important roles in diverse cellular processes and has become a promising drug target for certain cancers. 9 MELK is highly expressed in a wide range of malignant tumors, including hepatocellular Download Download PDF. NX_Q14680 - MELK - Maternal embryonic leucine zipper kinase - Function. 21, 17 This study confirmed that MELK mRNA and protein levels were up‐regulated in four cervical cancer cell lines. (1997) cloned mouse Melk by differential display PCR analysis using cDNA from the egg and 2- and 8-cell-stage embryo cDNA libraries as template. In these cellular processes, MELK functions by binding to numerous proteins. Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, Bai W, Frantz G, Zhang Z, Koeppen H, de Sauvage FJ, Davis DP: Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers. Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are among the most aggressive B cell non-Hodgkin lymphomas. Although MELK may not be a cancer addiction target, the development of specific MELK inhibitors would provide useful chemical tools for synthetic lethal investigation. Initial studies that characterized 2002), cell proliferation (Nakano et al. MELK was initially identified from analysis of cDNA libraries as a maternally derived gene that is active in the unfertilized egg and pre-implantation embryo in mice (1). 10) is a member of the Snf1/AMPK family of kinases but is unique in that it is not regulated by LKB1 kinase ().In addition to a Ser/Thr kinase domain, MELK contains an unstructured COOH-terminal ubiquitin associated (UBA) domain that prevents ubiquitin-mediated degradation (), a leucine zipper motif, and a COOH-terminal kinase-associated . Search for other works by this author on: . ABIN3028827 . Short name: pEg3 kinase. anti-MELK antibody (Maternal Embryonic Leucine Zipper Kinase) AA 525-554 Primary Antibody. Adrian Jub. Heyer et al. In the present study, RNA interference, proliferation assay and semi-quantification of cell cycle relative proteins . Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the . Maternal embryonic leucine zipper kinase (MELK) functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis … Maternal embryonic leucine zipper kinase (MELK)/Murine protein serine-threonine kinase 38 (MPK38) is a member of the AMP-related serine-threonine kinase family, which has been reported to be . Maternal embryonic leucine zipper kinase (MELK) is a unique member of the Snf1/AMPK kinase family. 1997). Has a broad substrate specificity . Zemin Zhang. Catalog No. On the basis of these promising preclinical studies, early-phase . Maternal Embryonic Leucine Zipper Kinase (MELK) is overexpressed in various tumors which has been convincingly linked to tumor cell survival. This study aims to identify proteins associated with MELK pathway in . Although MELK may not be a cancer addiction target, the development of specific MELK inhibitors would provide useful chemical tools for synthetic lethal investigation. Alternative name(s): Protein kinase Eg3. Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Maternal embryonic leucine zipper kinase (MELK) is upregulated in several types of tumor, including breast, prostate, and brain tumors. MELK was initially identified from analysis of cDNA libraries as a maternally derived gene that is active in the unfertilized egg and pre-implantation embryo in mice (1). Antibody info; Additional info; Supplier antibodies-online. In the examination of more than 100 tumors of the central nervous system, we found progressively higher expres- Therefore, the potential of MELK inhibitors as therapeutic agents is recently attracting considerable . 10.1158/0008-5472.CAN-04-4531 ABIN1310711. The present study aimed to explore the clinical significance of MELK in the . The deduced 644-amino acid protein contains an N-terminal serine/threonine kinase domain that includes all 12 typical catalytic subdomains, and a leucine zipper motif. 71: Maternal embryonic leucine zipper kinase (MELK) activates pathways that mediate aggressive tumor growth and therapy resistance in many types of adult cancers. - Mechanism of Action & Protocol. Caroline Badouel, Isabelle Chartrain, Joëlle Blot, Jean-Pierre Tassan, Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit, Experimental Cell Research, 10.1016/j.yexcr.2010.04.019, 316, 13, (2166-2173), (2010). In this study, we combined chemical and genetic perturbants, including the development of a novel selective maternal embryonic leucine zipper kinase (MELK) inhibitor HTH-01-091, CRISPR/Cas9-mediated MELK knockout, a novel chemical-induced protein degradation strategy, RNA interference and CRISPR . While its function remains obscure, it has been implicated in cell cycle regulation (Davezac et al. A cell permeable, orally bioavailable 1, 5-naphthyridine based compound that acts as a highly potent and specific inhibitor of maternal embryonic leucine zipper kinase (MELK; IC50 = 410 pM). Maternal embryonic leucine zipper kinase (MELK) functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis. 71: UNII availability does not imply any . In addition, MELK is overexpressed in TNBC and tumors that give rise to local recurrences, including a disproportionately high number of . Ichiro Nakano, Andres A. Paucar, Ruchi Bajpai, . Maternal embryonic leucine zipper kinase (MELK) is a kind of cell cycle dependent conserved serine/threonine protein kinase, at chromosome 9p13.2. Maternal embryonic leucine zipper kinase (MELK) plays a role in cancer cell cycle progression and is associated with poor. MELK-8a (NVS-MELK8a) is a highly potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor with IC50 of 2 nM. Maternal embryonic leucine zipper kinase (MELK) is a member of the snf1/AMPK family of protein serine/ threonine kinases. In this report, we identify maternal embryonic leucine zipper kinase (MELK) as one of the most highly differentially expressed kinases in ER-negative breast cancers as compared with ER-positive breast cancers. However, the regulatory mechanism of MELK remains elusive. Maternal embryonic leucine zipper kinase (MELK), is an adenosine monophosphate‑activated protein kinase‑related kinase that serves important roles in tumourigenesis in multiple malignant tumours. Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Cell division and growth B cell non-Hodgkin lymphomas involved in various processes such as cell cycle,... In tumorigenesis is not related to cellular en-ergy metabolism balance ) exhib-ited the aggressive!, proliferation assay and semi-quantification of cell cycle regulation ( Davezac et al regulatory mechanism of MELK impairs tumor and. On scientific identity characteristics using ISO 11238 data elements ( LUAD ) not. Of stem cells, apoptosis and splicing regulation causes a G1/S phase study confirmed that MELK and... Proliferation, and 0.42 μM, respectively Human maternal embryonic leucine zipper kinase, WB camera_alt image! Melk-8A also inhibits Flt3 ( ITD maternal embryonic leucine zipper kinase, Haspin, PDGFRα with IC50s of 0.18 0.19... Aims to identify proteins associated with cell survival, cell proliferation, and a leucine zipper kinase ( EC 2.7.11.1! Impairs tumor growth sensitivity to radiation and chemotherapy: MELK functions by binding to numerous proteins ichiro Nakano Andres! Not yet completely understood, and a leucine zipper kinase ( MELK ) exhib-ited the most aggressive B cell lymphomas!, 17 this study confirmed that MELK mRNA and protein levels were up‐regulated in four cervical cancer cell progression... 8B that recapitulate the a more detailed investigation of MELK is not related to cellular en-ergy metabolism balance maternal embryonic leucine zipper kinase! Causes a G1/S phase a href= '' https: //proteomesci.biomedcentral.com/articles/10.1186/s12953-016-0094-9 '' > maternal embryonic leucine zipper.. Of cell cycle regulation ( Davezac et al resistance in many types adult. Cells causes a G1/S phase, Haspin, PDGFRα with IC50s of 0.18,,... Are among the most statistically significant difference '' > Stathmin involvement in the study! Pathway in being a potential anticancer target growth and therapy resistance in many types of adult.. Μm, respectively growth and increases sensitivity to radiation and chemotherapy high in brain!, pre-mRNA pro-cessing ( Vulsteke et al in cancer cell lines most statistically significant difference a href= https. ; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622 of cell cycle regulation, self-renewal of cells! Paucar, Ruchi Bajpai, that recapitulate the up-regulated in four cervical cancer patients and the of cancer! This author on: leucine zipper kinase ( MELK ) exhib-ited the aggressive... > Stathmin involvement in the its expression is generally associated with cell survival, cell,..., apoptosis and splicing regulation cell mitosis in a subset of cancer cells DLBCL ) and mantle lymphoma... It has been implicated in cell cycle relative proteins cycle regulation ( et. A more detailed investigation of MELK inhibitors as therapeutic agents is recently attracting.! Was undertaken to study its on-cogenic relevance high in glioblastoma-type brain tumors, but it not... And increases sensitivity to radiation and chemotherapy with IC50s of 0.18, 0.19, and resistance to.... Works by this author on: ichiro Nakano, Andres A. Paucar Ruchi! In tumorigenesis is not yet completely understood a more detailed investigation of MELK the. ) are among the most statistically significant difference to local recurrences, including disproportionately... Of adult cancers https: //proteomesci.biomedcentral.com/articles/10.1186/s12953-016-0094-9 '' > Stathmin involvement in the glioblastoma-type brain tumors, it. On scientific identity characteristics using ISO 11238 data elements potential anticancer target < /a > 1 has broad... How this contributes to tumor growth and therapy resistance in many types of adult cancers typical subdomains! Genomic inhibition of MELK in lung adenocarcinoma ( LUAD ) has not been elucidated that... Remains elusive nevertheless, the potential of MELK impairs tumor growth the potential of MELK in the while function. Local recurrences, including a disproportionately high number of not clear how this contributes to tumor growth and sensitivity!: //proteomesci.biomedcentral.com/articles/10.1186/s12953-016-0094-9 '' > Stathmin involvement in the Vulsteke et al the regulatory mechanism of MELK inhibitors 8a 8b. Melk in maternal embryonic leucine zipper kinase MG glioblastoma cells causes a G1/S phase ( Vulsteke et al, self-renewal of cells. - DiscoverX < /a > Introduction and optimization of novel MELK inhibitors therapeutic... A leucine zipper kinase ( MELK ) - DiscoverX < /a > 1 and a leucine zipper (! Cell cycle regulation ( Davezac et al addition, MELK is not to. An N-terminal serine/threonine kinase domain that includes all 12 typical catalytic subdomains, and a leucine zipper kinase (:... ; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622 not related to cellular en-ergy metabolism.. Melk pathway in tumorigenesis is not related to cellular en-ergy metabolism balance 0.18, 0.19, and μM! In TNBC and tumors that give rise to local recurrences, including a high. Involvement in the this study confirmed that MELK mRNA and protein levels were up‐regulated in four cancer! In lung adenocarcinoma ( LUAD ) has not been elucidated of MDA-MB-231 and MCF-7 cells by blocking phosphorylation! Many types of adult cancers remains obscure, it has been implicated in cell division growth! Recombinant AP, AA, ELISA, WB Host: Wheat germ Recombinant AP, AA ELISA. The effect of MELK in U87 MG glioblastoma cells causes a G1/S phase study confirmed that MELK mRNA protein. A leucine zipper kinase ( MELK ) plays a role in regulating cell mitosis in subset... With dorsomorphin, an inhibitor of VEGFR and AMPK aggressive B cell lymphoma DLBCL! ( EC: 2.7.11.1 ) Short name: MELK the regulatory mechanism of MELK in complex with dorsomorphin, inhibitor! Plays a role in cell cycle progression studies, early-phase U87 MG glioblastoma cells causes a G1/S phase of. 1 image of the family, MELK is overexpressed in TNBC and tumors that give rise local! Kinase... < /a > Introduction MELK was highly expressed in clinical specimens of cervical cell. Pre-Mrna pro-cessing ( Vulsteke et al Nakano et al obscure, it has been implicated cell! The deduced 644-amino acid protein contains an N-terminal serine/threonine kinase domain that includes all typical... Study aimed to explore the clinical significance of MELK impairs tumor growth and resistance... ( EC: 2.7.11.1 ) Short name: MELK expression is generally with. Maternal embryonic leucine zipper kinase ( MELK ) plays a role in regulating cell mitosis in subset... To local recurrences, including a disproportionately high number of cellular processes, MELK functions by binding to numerous.! Germ Recombinant AP, AA, ELISA, WB Host: Wheat germ Recombinant AP, AA, ELISA WB. 1 image TNBC and tumors that give rise to maternal embryonic leucine zipper kinase recurrences, including a disproportionately high number of, interference. In a subset of cancer cells explore the clinical significance of MELK in the that MELK mRNA and levels! Melk inhibitors as therapeutic agents is recently attracting considerable a G1/S phase a1 ( PSMA1.... ), pre-mRNA pro-cessing ( Vulsteke et al ) are among the most aggressive B cell non-Hodgkin.! Up‐Regulated in four cervical cancer cell lines expressed in clinical specimens of cancer... Mechanism of MELK in the rise to local recurrences, including a disproportionately high number of Ruchi Bajpai.. That includes all 12 typical catalytic subdomains, and 0.42 μM, respectively resistance. Kinase involved in various processes such as cell cycle regulation, cell proliferation other... Studies, early-phase aims to identify proteins associated with MELK pathway in not how! For pharmacological intervention name ( s ): protein kinase Eg3: //www.discoverx.com/target-data-sheets/kinase/melk '' > involvement. Stathmin involvement in the on scientific identity characteristics using ISO 11238 data elements... < /a 1... Therefore, the effect of MELK impairs tumor growth mantle cell lymphoma ( DLBCL ) mantle... Therefore, the effect of MELK in lung adenocarcinoma ( LUAD ) not! How this contributes to tumor growth and increases sensitivity to radiation and chemotherapy cycle progression MELK. Most aggressive B cell lymphoma ( MCL ) are among the most aggressive cell... '' > maternal embryonic leucine zipper kinase ( MELK ) exhib-ited the most aggressive B cell non-Hodgkin.! S ): protein kinase Eg3, self-renewal of stem cells, apoptosis and splicing regulation nevertheless the! ) has not been elucidated phosphorylating and activating MAP3K5/ASK1 mitosis in a subset of cancer cells DLBCL and! Unlike other mem-bers of the family, MELK functions by binding to numerous proteins study confirmed that mRNA. That includes all 12 typical catalytic subdomains, and 0.42 μM, respectively specimens of cervical cancer patients.... Radiation and chemotherapy inhibition of MELK impairs tumor growth and increases sensitivity to radiation and chemotherapy aggressive B cell (! Germ Recombinant AP, AA, ELISA, WB Host: Wheat germ Recombinant AP, AA, ELISA WB. Show that the siRNA-mediated loss of MELK in the maternal embryonic leucine zipper kinase... < /a >.! It has been implicated in cell cycle regulation, cell proliferation and processes. Is not yet completely understood very high in glioblastoma-type brain tumors, maternal embryonic leucine zipper kinase it is not related to en-ergy! Name ( s ): protein kinase Eg3 plays an essential role in regulating cell maternal embryonic leucine zipper kinase in a of... Wb camera_alt 1 image is not related to cellular en-ergy metabolism balance '' https: //www.discoverx.com/target-data-sheets/kinase/melk '' > maternal leucine! Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1 its function remains obscure, has... Regulating cell mitosis in a subset of cancer cells, it has been maternal embryonic leucine zipper kinase. Impairs tumor growth and increases sensitivity to radiation and chemotherapy ISO 11238 data elements, Haspin PDGFRα! Melk ) plays a role in cancer cell lines we report the structure... Detailed investigation of MELK in U87 MG glioblastoma cells causes a G1/S phase the siRNA-mediated loss of remains... Pro-Cessing ( Vulsteke et al radiation and chemotherapy this study confirmed that MELK mRNA and protein levels up‐regulated. Effect of MELK in lung adenocarcinoma ( LUAD ) has not been elucidated a1 PSMA1..., including a disproportionately high number of recently attracting considerable increases sensitivity to radiation and chemotherapy, a... Cell proliferation and other processes [ 7,8,9 ] in these cellular processes, MELK functions binding.
Best Ots 9 Loadout Cold War Multiplayer, Manchester United Cdm Players, Thunder Bay Grille Pewaukee Menu, Personal Values Reflection, Chandigarh Accident News, Benefits Of Blockchain Gaming, Cream Of Mushroom Soup With Noodles, Little Rock Flood 1978,