Computational Approach to Identify Mutations in Genes of Notch Signaling Pathway and Its Association with OSCC
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MAML1 Antibody A
Revision 1 C 0 2 - t MAML1 Antibody a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 8 0 Web: [email protected] 6 www.cellsignal.com 4 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source: UniProt ID: Entrez-Gene Id: WB, IP H Endogenous 130 Rabbit Q92585 9794 Product Usage Information Application Dilution Western Blotting 1:1000 Immunoprecipitation 1:50 Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity MAML1 Antibody detects endogenous levels of total MAML1 protein. It does not cross- react with MAML2 and MAML3. Species Reactivity: Human Source / Purification Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding His811 of human MAML1. Antibodies are purified by protein A and peptide affinity chromatography. Background Mastermind-like (MAML) family of proteins are homologs of Drosophila Mastermind. The family is composed of three members in mammals: MAML1, MAML2, and MAML3 (1,2). MAML proteins form complexes with the intracellular domain of Notch (ICN) and the transcription factor CSL (RBP-Jκ) to regulate Notch target gene expression (3-5). MAML1 also interacts with myocyte enhancer factor 2C (MEF2C) to regulate myogenesis (6). MAML2 is frequently found to be fused with Mucoepidermoid carcinoma translocated gene 1 (MECT1, also know as WAMTP1 or TORC1) in patients with mucoepidermoid carcinomas and Warthin's tumors (7). -
Mdm2-Mediated Ubiquitylation: P53 and Beyond
Cell Death and Differentiation (2010) 17, 93–102 & 2010 Macmillan Publishers Limited All rights reserved 1350-9047/10 $32.00 www.nature.com/cdd Review Mdm2-mediated ubiquitylation: p53 and beyond J-C Marine*,1 and G Lozano2 The really interesting genes (RING)-finger-containing oncoprotein, Mdm2, is a promising drug target for cancer therapy. A key Mdm2 function is to promote ubiquitylation and proteasomal-dependent degradation of the tumor suppressor protein p53. Recent reports provide novel important insights into Mdm2-mediated regulation of p53 and how the physical and functional interactions between these two proteins are regulated. Moreover, a p53-independent role of Mdm2 has recently been confirmed by genetic data. These advances and their potential implications for the development of new cancer therapeutic strategies form the focus of this review. Cell Death and Differentiation (2010) 17, 93–102; doi:10.1038/cdd.2009.68; published online 5 June 2009 Mdm2 is a key regulator of a variety of fundamental cellular has also emerged from recent genetic studies. These processes and a very promising drug target for cancer advances and their potential implications for the development therapy. It belongs to a large family of (really interesting of new cancer therapeutic strategies form the focus of this gene) RING-finger-containing proteins and, as most of its review. For a more detailed discussion of Mdm2 and its other members, Mdm2 functions mainly, if not exclusively, as various functions an interested reader should also consult an E3 ligase.1 It targets various substrates for mono- and/or references9–12. poly-ubiquitylation thereby regulating their activities; for instance by controlling their localization, and/or levels by The p53–Mdm2 Regulatory Feedback Loop proteasome-dependent degradation. -
Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease
Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 654637, 10 pages http://dx.doi.org/10.1155/2015/654637 Research Article Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease Rosario Gulino,1,2 Rosalba Parenti,1 and Massimo Gulisano1 1 Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 64, 95127 Catania, Italy 2IOM Ricerca s.r.l., Via Penninazzo 11, 95029 Viagrande, Italy Correspondence should be addressed to Rosario Gulino; [email protected] Received 26 September 2014; Accepted 16 December 2014 Academic Editor: Andrea Vecchione Copyright © 2015 Rosario Gulino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A hopeful spinal cord repairing strategy involves the activation of neural precursor cells. Unfortunately, their ability to generate neurons after injury appears limited. Another process promoting functional recovery is synaptic plasticity. We have previously studied some mechanisms of spinal plasticity involving BDNF, Shh, Notch-1, Numb, and Noggin, by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin. TDP-43 is a nuclear RNA/DNA binding protein involved in amyotrophic lateral sclerosis. Interestingly, TDP-43 could be localized at the synapse and affect synaptic strength. Here, we would like to deepen the investigation of this model of spinal plasticity. After lesion, we observed a glial reaction and an activity-dependent modification of Shh, Noggin, and Numb proteins. By using multivariate regression models, we found that Shh and Noggin could affect motor performance and that these proteins could be associated with both TDP-43 and Numb. -
1 Small-Molecule Targeting of MUSASHI RNA-Binding Activity in Acute Myeloid Leukemia 2 3 Gerard Minuesa1, Steven K
bioRxiv preprint doi: https://doi.org/10.1101/321174; this version posted May 14, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia 2 3 Gerard Minuesa1, Steven K. Albanese2,3, Arthur Chow1, Alexandra Schurer1, Sun-Mi Park1, 4 Christina Z. Rotsides4, James Taggart1, Andrea Rizzi3,5, Levi N. Naden3, Timothy Chou1, Saroj 5 Gourkanti1, Daniel Cappel6, Maria C. Passarelli3,7, Lauren Fairchild3,8, Carolina Adura9, J Fraser 6 Glickman9, Jessica Schulman10, Christopher Famulare11, Minal Patel11, Joseph K. Eibl12, Gregory 7 M. Ross12, Derek Tan4, Christina Leslie3, Thijs Beuming13, Yehuda Goldgur14, John D. Chodera3, 8 Michael G. Kharas1,* 9 10 1. Molecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem 11 Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA 12 2. Louis V. Gerstner Jr. Graudate School of Biomedical Sciences, Memorial Sloan Kettering 13 Cancer Center, New York, NY, 10065, USA 14 3. Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan 15 Kettering Cancer Center, New York, NY, 10065, USA 16 4. Chemical Biology Program and Tri-Institutional Research Program, Memorial Sloan Kettering 17 Cancer Center, 1275 York Avenue, Box 422, New York, New York, NY, 10065, USA 18 5. Tri-Institutional Training Program in Computational Biology and Medicine, New York, NY, 19 10065, USA 20 6. Schrödinger GmbH, Q7, 23, 68161 Mannheim, Germany 21 7. Weill Cornell Medical College, Rockefeller University & Sloan Kettering Institute Tri-Institutional 22 MD-PhD Program, New York, NY, 10065, USA 23 8. -
Cystatin-B Negatively Regulates the Malignant Characteristics of Oral Squamous Cell Carcinoma Possibly Via the Epithelium Proliferation/ Differentiation Program
ORIGINAL RESEARCH published: 24 August 2021 doi: 10.3389/fonc.2021.707066 Cystatin-B Negatively Regulates the Malignant Characteristics of Oral Squamous Cell Carcinoma Possibly Via the Epithelium Proliferation/ Differentiation Program Tian-Tian Xu 1, Xiao-Wen Zeng 1, Xin-Hong Wang 2, Lu-Xi Yang 1, Gang Luo 1* and Ting Yu 1* 1 Department of Periodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China, 2 Department of Oral Pathology and Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China Disturbance in the proteolytic process is one of the malignant signs of tumors. Proteolysis Edited by: Eva Csosz, is highly orchestrated by cysteine cathepsin and its inhibitors. Cystatin-B (CSTB) is a University of Debrecen, Hungary general cysteine cathepsin inhibitor that prevents cysteine cathepsin from leaking from Reviewed by: lysosomes and causing inappropriate proteolysis. Our study found that CSTB was Csongor Kiss, downregulated in both oral squamous cell carcinoma (OSCC) tissues and cells University of Debrecen, Hungary Gergely Nagy, compared with normal controls. Immunohistochemical analysis showed that CSTB was University of Debrecen, Hungary mainly distributed in the epithelial structure of OSCC tissues, and its expression intensity *Correspondence: was related to the grade classification. A correlation analysis between CSTB and clinical Gang Luo [email protected] prognosis was performed using gene expression data and clinical information acquired Ting Yu from The Cancer Genome Atlas (TCGA) database. Patients with lower expression levels of [email protected] CSTB had shorter disease-free survival times and poorer clinicopathological features Specialty section: (e.g., lymph node metastases, perineural invasion, low degree of differentiation, and This article was submitted to advanced tumor stage). -
Musashi RNA-Binding Proteins As Cancer Drivers and Novel Therapeutic Targets Alexander E
Published OnlineFirst January 31, 2017; DOI: 10.1158/1078-0432.CCR-16-2728 Review Clinical Cancer Research Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets Alexander E. Kudinov1, John Karanicolas1, Erica A. Golemis1, and Yanis Boumber1,2 Abstract Aberrant gene expression that drives human cancer can arise mRNA stability and translation of proteins operating in essential from epigenetic dysregulation. Although much attention has oncogenic signaling pathways, including NUMB/Notch, PTEN/ focused on altered activity of transcription factors and chroma- mTOR, TGFb/SMAD3, MYC, cMET, and others. On the basis of tin-modulating proteins, proteins that act posttranscriptionally these activities, MSI proteins maintain cancer stem cell popula- can potently affect expression of oncogenic signaling proteins. tions and regulate cancer invasion, metastasis, and development The RNA-binding proteins (RBP) Musashi-1 (MSI1) and Musashi- of more aggressive cancer phenotypes, including drug resistance. 2 (MSI2) are emerging as regulators of multiple critical biological Although RBPs are viewed as difficult therapeutic targets, initial processes relevant to cancer initiation, progression, and drug efforts to develop MSI-specific inhibitors are promising, and RNA resistance. Following identification of Musashi as a regulator of interference–based approaches to inhibiting these proteins have progenitor cell identity in Drosophila, the human Musashi proteins had promising outcomes in preclinical studies. In the interim, were initially linked to control of maintenance of hematopoietic understanding the function of these translational regulators may stem cells, then stem cell compartments for additional cell types. yield insight into the relationship between mRNA expression and More recently, the Musashi proteins were found to be overex- protein expression in tumors, guiding tumor-profiling analysis. -
NUMB and NUMBL Differences in Gene Regulation
www.impactjournals.com/oncotarget/ Oncotarget, 2018, Vol. 9, (No. 10), pp: 9219-9234 Research Paper NUMB and NUMBL differences in gene regulation José Manuel García-Heredia1,2,3 and Amancio Carnero1,3 1Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Seville, Spain 2Department of Vegetal Biochemistry and Molecular Biology, University of Seville, Seville, Spain 3CIBER de Cáncer, Instituto de Salud Carlos III, Pabellón 11, Planta 0, Madrid, Spain Correspondence to: Amancio Carnero, email: [email protected] Keywords: NUMB; NUMBL; cancer; Notch pathway; WNT pathway Received: September 06, 2017 Accepted: January 03, 2018 Published: January 11, 2018 Copyright: García-Heredia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT NUMB, and its close homologue NUMBL, behave as tumor suppressor genes by regulating the Notch pathway. The downregulation of these genes in tumors is common, allowing aberrant Notch pathway activation and tumor progression. However, some known differences between NUMB and NUMBL have raised unanswered questions regarding the redundancy and/or combined regulation of the Notch pathway by these genes during the tumorigenic process. We have found that NUMB and NUMBL exhibit mutual exclusivity in human tumors, suggesting that the associated tumor suppressor role is regulated by only one of the two proteins in a specific cell, avoiding duplicate signaling and simplifying the regulatory network. We have also found differences in gene expression due to NUMB or NUMBL downregulation. -
Selenite Inhibits Notch Signaling in Cells and Mice
International Journal of Molecular Sciences Article Selenite Inhibits Notch Signaling in Cells and Mice Michael Powers 1, Liu Liu 1, Dane Deemer 1, Selina Chen 1, Aaron Scholl 1, Masafumi Yoshinaga 2 and Zijuan Liu 1,* 1 Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA; [email protected] (M.P.); [email protected] (L.L.); [email protected] (D.D.); [email protected] (S.C.); [email protected] (A.S.) 2 Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA; myoshina@fiu.edu * Correspondence: [email protected]; Tel.: +1-248-370-3554 Abstract: Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have shown selectively higher affinity and toxicity towards cancer cells, highlighting their potential to serve as chemotherapeutic agents or adjuvants. At varying doses, selenite extensively regulates cellular signaling and modulates many cellular processes. In this study, we report the identification of Delta–Notch signaling as a previously uncharacterized selenite inhibited target. Our transcriptomic results in selenite treated primary mouse hepatocytes revealed that the tran- scription of Notch1, Notch2, Hes1, Maml1, Furin and c-Myc were all decreased following selenite treatment. We further showed that selenite can inhibit Notch1 expression in cultured MCF7 breast adenocarcinoma cells and HEPG2 liver carcinoma cells. In mice acutely treated with 2.5 mg/kg Citation: Powers, M.; Liu, L.; selenite via intraperitoneal injection, we found that Notch1 expression was drastically lowered in Deemer, D.; Chen, S.; Scholl, A.; liver and kidney tissues by 90% and 70%, respectively. -
Identification and Preliminary Functional Analysis of Alternative Splicing of Siah1 in Xenopus Laevis
Biochemical and Biophysical Research Communications 396 (2010) 419–424 Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc Identification and preliminary functional analysis of alternative splicing of Siah1 in Xenopus laevis Luan Wen a,b, Jiantao Liu a,c, Yonglong Chen a, Donghai Wu a,* a Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Road, Guangzhou Science Park, 510530 Guangzhou, China b Graduate University of Chinese Academy of Sciences, 100049 Beijing, China c Laboratory of Veterinary Pharmacology, College of Veterinary Medicine South China Agricultural University, Guangzhou, China article info abstract Article history: Siah proteins are vertebrate homologs of the Drosophila ‘seven in absentia’ gene. In this study, we char- Received 11 April 2010 acterized two splicing forms, Siah1a and Siah1b, of the Xenopus seven in absentia homolog 1 gene (Siah1). Available online 22 April 2010 Overexpression of xSiah1a led to severe suppression of embryo cleavage, while that of xSiah1b was not effective even at a high dose. Competition analysis demonstrated that co-expression of xSiah1a and 1b Keywords: generated the same phenotype as overexpression of xSiah1a alone, suggesting that xSiah1b does not Xenopus interfere with the function of xSiah1a. Since xSiah1b has an additional 31 amino acids in the N-terminus xSiah1a compared to xSiah1a, progressive truncation of xSiah1b from the N-terminus showed that inability of xSiah1b xSiah1b to affect embryo cleavage was associated with the length of the N-terminal extension of extra amino acids. The possible implication of this finding is discussed. -
Anti-MAML1 (Aa 655-754) Polyclonal Antibody (DPAB-DC3896) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
Anti-MAML1 (aa 655-754) polyclonal antibody (DPAB-DC3896) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Antigen Description This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway. Immunogen MAML1 (NP_055572, 655 a.a. ~ 754 a.a) partial recombinant protein with GST tag. The sequence is AEQEKQQFQRHLTRPPPQYQDPTQGSFPQQVGQFTGSSAAVPGMNTLGPSNSSCPRVFPQA GNLMPMGPGHASVSSLPTNSGQQDRGVAQFPGSQNMPQS Source/Host Mouse Species Reactivity Human Conjugate Unconjugated Applications WB (Recombinant protein), ELISA, Size 50 μl Buffer 50 % glycerol Preservative None Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. GENE INFORMATION Gene Name MAML1 mastermind-like 1 (Drosophila) [ Homo sapiens (human) ] Official Symbol MAML1 Synonyms MAML1; mastermind-like 1 (Drosophila); Mam1; Mam-1; mastermind-like protein 1; mastermind homolog; 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved Entrez Gene ID 9794 Protein Refseq NP_055572 UniProt ID Q92585 Chromosome Location 5q35 Pathway Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants; Delta-Notch Signaling Pathway; FBXW7 Mutants and NOTCH1 in Cancer; Generic Transcription Pathway Function peptide antigen binding; protein binding; protein kinase binding; transcription coactivator activity 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 2 © Creative Diagnostics All Rights Reserved. -
Numb−/Low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling
Published OnlineFirst July 27, 2017; DOI: 10.1158/1078-0432.CCR-17-0913 Biology of Human Tumors Clinical Cancer Research NumbÀ/low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling Yanjing Guo1, Kai Zhang2, Chaping Cheng2, Zhongzhong Ji2, Xue Wang2, Minglei Wang1, Mingliang Chu1, Dean G. Tang3, Helen He Zhu1, and Wei-Qiang Gao1,2 Abstract Purpose: To elucidate the role and molecular mechanism of Results: We show here that Numb was downregulated and Numb in prostate cancer and the functional contribution of negatively correlated with prostate cancer advancement. Func- À Numb /low prostate cancer cells in castration resistance. tionally, Numb played an inhibitory role in xenograft prostate Experimental Design: The expression of Numb was assessed tumor growth and castration-resistant prostate cancer develop- using multiple Oncomine datasets and prostate cancer tissues ment by suppressing Notch and Hedgehog signaling. Using from both humans and mice. The biological effects of the a Numb promoter–based lentiviral reporter system, we were able À overexpression and knockdown of Numb in human prostate to distinguish Numb /low prostate cancer cells from Numbhigh À cancer cell lines were investigated in vitro and in vivo.In cells. Numb /low prostate cancer cells were smaller and quiescent, addition, we developed a reliable approach to distinguish preferentially expressed Notch and Hedgehog downstream and between prostate cancer cell populations with a high or low stem-cell–associated genes, and associated with a greater resis- endogenous expression of Numb protein using a Numb pro- tance to ADT. The inhibition of the Notch and Hedgehog signal- À moter–based lentiviral reporter system. -
NUMB Enhances Notch Signaling by Repressing Ubiquitination of NOTCH1 Intracellular Domain
doi:10.1093/jmcb/mjz088 Journal of Molecular Cell Biology (2020), 12(5), 345–358 | 345 Published online September 3, 2019 Article NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain Zhiyuan Luo†,LiliMu†, Yue Zheng, Wenchen Shen, Jiali Li, Lichao Xu, Bo Zhong, Ying Liu*, and Yan Zhou * College of Life Sciences, Renmin Hospital of Wuhan University, Medical Research Institute at School of Medicine, Wuhan University, Wuhan 430072, China † These authors contributed equally to this work. * Correspondence to: Ying Liu, E-mail: [email protected]; Yan Zhou, E-mail: [email protected] Edited by Zhen-Ge Luo The release and nuclear translocation of the intracellular domain of Notch receptor (NICD) is the prerequisite for Notch signaling- mediated transcriptional activation. NICD is subjected to various posttranslational modifications including ubiquitination. Here, we surprisingly found that NUMB proteins stabilize the intracellular domain of NOTCH1 receptor (N1ICD) by regulating the ubiquitin– proteasome machinery, which is independent of NUMB’s role in modulating endocytosis. BAP1, a deubiquitinating enzyme (DUB), was further identified as a positive N1ICD regulator, and NUMB facilitates the association between N1ICD and BAP1 to stabilize N1ICD. Intriguingly, BAP1 stabilizes N1ICD independent of its DUB activity but relying on the BRCA1-inhibiting function. BAP1 strengthens Notch signaling and maintains stem-like properties of cortical neural progenitor cells. Thus, NUMB enhances Notch signaling by regulating the ubiquitinating activity of the BAP1–BRCA1 complex. Keywords: NUMB, Notch intracellular domain, BAP1, ubiquitination, neural progenitor cells Introduction enzymes (DUBs) have been reported to regulate their turnover Diversifying cell fates during animal development requires and activities (Le Bras et al., 2011; Moretti and Brou, 2013).