Functional Relationship Between Merlin and the ERM Proteins
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Machine-Learning and Chemicogenomics Approach Defi Nes and Predicts Cross-Talk of Hippo and MAPK Pathways
Published OnlineFirst November 18, 2020; DOI: 10.1158/2159-8290.CD-20-0706 RESEARCH ARTICLE Machine -Learning and Chemicogenomics Approach Defi nes and Predicts Cross-Talk of Hippo and MAPK Pathways Trang H. Pham 1 , Thijs J. Hagenbeek 1 , Ho-June Lee 1 , Jason Li 2 , Christopher M. Rose 3 , Eva Lin 1 , Mamie Yu 1 , Scott E. Martin1 , Robert Piskol 2 , Jennifer A. Lacap 4 , Deepak Sampath 4 , Victoria C. Pham 3 , Zora Modrusan 5 , Jennie R. Lill3 , Christiaan Klijn 2 , Shiva Malek 1 , Matthew T. Chang 2 , and Anwesha Dey 1 ABSTRACT Hippo pathway dysregulation occurs in multiple cancers through genetic and non- genetic alterations, resulting in translocation of YAP to the nucleus and activation of the TEAD family of transcription factors. Unlike other oncogenic pathways such as RAS, defi ning tumors that are Hippo pathway–dependent is far more complex due to the lack of hotspot genetic alterations. Here, we developed a machine-learning framework to identify a robust, cancer type–agnostic gene expression signature to quantitate Hippo pathway activity and cross-talk as well as predict YAP/TEAD dependency across cancers. Further, through chemical genetic interaction screens and multiomics analyses, we discover a direct interaction between MAPK signaling and TEAD stability such that knockdown of YAP combined with MEK inhibition results in robust inhibition of tumor cell growth in Hippo dysregulated tumors. This multifaceted approach underscores how computational models combined with experimental studies can inform precision medicine approaches including predictive diagnostics and combination strategies. SIGNIFICANCE: An integrated chemicogenomics strategy was developed to identify a lineage- independent signature for the Hippo pathway in cancers. -
Activated Ezrin Controls MISP Levels to Ensure Correct Numa Polarization and Spindle Orientation Yvonne T
© 2018. Published by The Company of Biologists Ltd | Journal of Cell Science (2018) 131, jcs214544. doi:10.1242/jcs.214544 RESEARCH ARTICLE Activated ezrin controls MISP levels to ensure correct NuMA polarization and spindle orientation Yvonne T. Kschonsak1,2 and Ingrid Hoffmann1,* ABSTRACT misregulation in spindle orientation can result in disorganized tissue Correct spindle orientation is achieved through signaling pathways that morphology due to cell multi-layering, which could be associated provide a molecular link between the cell cortex and spindle with the earliest cancer developments (McCaffrey and Macara, microtubules in an F-actin-dependent manner. A conserved cortical 2011; Pease and Tirnauer, 2011). protein complex, composed of LGN (also known as GPSM2), NuMA The precise spindle position and orientation in the cell is achieved (also known as NUMA1) and dynein–dynactin, plays a key role in by signaling pathways generating pulling and pushing forces on the establishing proper spindle orientation. It has also been shown that the spindle, both externally or internally (Gönczy, 2002; Grill and actin-binding protein MISP and the ERM family, which are activated by Hyman, 2005; Théry et al., 2005; Fink et al., 2011). The longest lymphocyte-oriented kinase (LOK, also known as STK10) and Ste20- established player in spindle orientation is the conserved ternary α like kinase (SLK) (hereafter, SLK/LOK) in mitosis, regulate spindle complex, composed of G i, Leu-Gly-Asn repeat-enriched protein orientation. Here, we report that MISP functions downstream of the (LGN, also known as GPSM2) and nuclear mitotic apparatus ERM family member ezrin and upstream of NuMA to allow optimal (NuMA, also known as NUMA1) (Du et al., 2001; Du and Macara, α spindle positioning. -
Expression of Ezrin, CD44, and VEGF in Giant Cell Tumor of Bone and Its
Zhang et al. World Journal of Surgical Oncology (2015) 13:168 DOI 10.1186/s12957-015-0579-5 WORLD JOURNAL OF SURGICAL ONCOLOGY RESEARCH Open Access Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance Jing Zhang1†, Jian Dong1†, Zuozhang Yang1*†, Xiang Ma1†, Jinlei Zhang1†, Mei Li2, Yun Chen2, Yingying Ding3, Kun Li3 and Zhiping Zhang3 Abstract Background: This research aimed to study the role of ezrin, CD44, and VEGF in invasion, metastasis, recurrence, and prognosis of giant cell tumor of bone (GCTB) and its association with the clinical and pathological features of GCTB. Methods: Expression status of ezrin, CD44, and VEGF in 80 GCTB tissues and its adjacent noncancerous tissue samples were measured with immunohistochemical and Elivison staining. Their correlation with the clinical and pathologic factors was statistically analyzed by chi-square test. Results: The expression status of ezrin, CD44, and VEGF were significantly higher in GCTB tissue samples than in its adjacent noncancerous tissue samples and in GCTB at Campanacci stage III than in Campanacci stages I and II (P < 0.05). No significant difference was found in age and sex of the patients and locations of the tumor (P > 0.05). Survival analysis showed that the expression status of ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB were positively associated with the survival rate of GCTB patients and negatively associated with ezrin and Campanacci stages of GCTB, indicating that ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB are the independent factors for GCTB. Conclusions: Ezrin, CD44, and VEGF are over-expressed in GCTB tissue and its adjacent noncancerous tissue samples and may play an important role in the occurrence, invasion, metastasis, and recurrence of GCTB. -
Feeling the Force: Role of Amotl2 in Normal Development and Cancer
Department of Oncology and Pathology Karolinska Institute, Stockholm, Sweden FEELING THE FORCE: ROLE OF AMOTL2 IN NORMAL DEVELOPMENT AND CANCER Aravindh Subramani Stockholm 2019 All previously published papers were reproduced with permission from the publisher. Front cover was modified from ©Renaud Chabrier and illustrated by Yu-Hsuan Hsu Published by Karolinska Institute. Printed by: US-AB Stockholm © Aravindh Subramani, 2019 ISBN 978-91-7831-426-3 Feeling the force: Role of AmotL2 in normal development and cancer. THESIS FOR DOCTORAL DEGREE (Ph.D.) J3:04, Torsten N Wiesel, U410033310, Bioclinicum, Karolinska University Hospital, Solna, Stockholm Friday, April 12th, 2019 at 13:00 By Aravindh Subramani Principal Supervisor: Opponent: Professor. Lars Holmgren Professor. Marius Sudol Karolinska Institute National University of Singapore Department of Oncology-Pathology Mechanobiology Institute (MBI) Co-supervisor(s): Examination Board: Docent. Jonas Fuxe Docent. Kaisa Lehti Karolinska Institute Karolinska institute Department of Microbiology, Tumor and Cell Department of Microbiology and Tumor Biology Biology (MTC) center (MTC) Associate Professor. Johan Hartman Docent. Ingvar Ferby Karolinska Institute Uppsala University Department of Oncology-Pathology Department of Medical Biochemistry and Microbiology Docent. Mimmi Shoshan Karolinska Institute Department of Oncology-Pathology To my mom and dad “Real knowledge is to know the extent of one's ignorance.” (Confucius) ABSTRACT Cells that fabricate the body, dwell in a very heterogeneous environment. Self-organization of individual cells into complex tissues and organs at the time of growth and revival is brought about by the combinatory action of biomechanical and biochemical signaling processes. Tissue generation and functional organogenesis, requires distinct cell types to unite together and associate with their corresponding microenvironment in a spatio-temporal manner. -
Adhesion Transendothelial Migration Without Affecting VCAM-1 Inhibits
An Antibody to the Sixth Ig-like Domain of VCAM-1 Inhibits Leukocyte Transendothelial Migration without Affecting Adhesion This information is current as of September 28, 2021. Sukmook Lee, Il-Hee Yoon, Aerin Yoon, Joan M. Cook-Mills, Chung-Gyu Park and Junho Chung J Immunol published online 1 October 2012 http://www.jimmunol.org/content/early/2012/10/01/jimmun ol.1103803 Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 28, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published October 1, 2012, doi:10.4049/jimmunol.1103803 The Journal of Immunology An Antibody to the Sixth Ig-like Domain of VCAM-1 Inhibits Leukocyte Transendothelial Migration without Affecting Adhesion Sukmook Lee,*,1,2 Il-Hee Yoon,*,†,1 Aerin Yoon,‡ Joan M. Cook-Mills,x Chung-Gyu Park,†,3 and Junho Chung‡,3 VCAM-1 plays a key role in leukocyte trafficking during inflammatory responses. -
Polarity: Merlin and Ezrin Get Organized
RESEARCH HIGHLIGHTS Nature Reviews Cancer | AOP, published online 10 January 2013; doi:10.1038/nrc3453 POLARITY Merlin and ezrin get organized The ezrin, radixin and moesin (ERM) proteins and the closely related tumour suppressor neuro fibromatosis type 2 (NF2; also known as merlin) function as scaffolds to organize the cell cortex localization and to help regulate cell polarity of ezrin all during epithelial morphogenesis, around the cell cortex. a process that is often disrupted in Therefore, NF2 seems to tumorigenesis. However, how NF2 be involved in restricting the and the ERM proteins achieve this localization of ezrin, a process organization, and the functional that the authors found requires relationship among these proteins, is α-catenin; this is interesting as it not completely clear. indicates a junction-independent Andrea McClatchey and col function for α-catenin. leagues followed the localization of Given the connections of the ezrin and NF2 during the establish ezrin cap to the cell cycle, the authors ment of apical–basal polarity in also examined the centrosomes and Lara Crow/NPG single Caco2 intestinal epithelial cells mitotic spindle position in single embedded in Matrigel. They noted Caco2 cells; they found that their (these mice eventually develop renal that ezrin became restricted into localization was tightly correlated carcinomas), and ectopic ezrin a cap-like structure at the plasma with the ezrin cap. Supporting this, localization and multi-layering in the membrane prior to the first cell centrosomes in cells expressing NF2 colon. In addition, cancer cells often division. The cells were uniformly shRNA were found near areas of have extra centrosomes; these can surrounded by extracellular matrix the cortex with ectopic ezrin, and be clustered to allow the cell to form and the cap lacked markers of apical spindles were aberrantly oriented in bipolar spindles, but loss of clustering polarity, indicating that intrinsic these cells. -
And Heterotypic Interaction of Merlin and Ezrin
Journal of Cell Science 112, 895-904 (1999) 895 Printed in Great Britain © The Company of Biologists Limited 1999 JCS0140 Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin Mikaela Grönholm1,*, Markku Sainio1, Fang Zhao1, Leena Heiska1, Antti Vaheri2 and Olli Carpén1 Departments of 1Pathology and 2Virology, University of Helsinki, Haartman Institute, PO Box 21 (Haartmaninkatu 3), FIN-00014 Helsinki *Author for correspondence (e-mail: mikaela.gronholm@helsinki.fi) Accepted 23 December 1998; published on WWW 25 February 1999 SUMMARY Ezrin, radixin and moesin (ERM) are homologous proteins, involves interaction between the amino- and carboxy- which are linkers between plasma membrane components termini. The amino-terminal association domain of merlin and the actin-containing cytoskeleton. The ERM protein involves residues 1-339 and has similar features with the family members associate with each other in a homotypic amino-terminal association domain of ezrin. The carboxy- and heterotypic manner. The neurofibromatosis 2 (NF2) terminal association domain cannot be mapped as precisely tumor suppressor protein merlin (schwannomin) is as in ezrin, but it requires residues 585-595 and a more structurally related to ERM members. Merlin is involved amino-terminal segment. Unlike ezrin, merlin does not in tumorigenesis of NF2-associated and sporadic require activation for self-association but native merlin schwannomas and meningiomas, but the tumor suppressor molecules can interact with each other. Heterodimerization mechanism is poorly understood. We have studied the between merlin and ezrin, however, occurs only following ability of merlin to self-associate and bind ezrin. Ezrin was conformational alterations in both proteins. -
The Role of the C-Terminus Merlin in Its Tumor Suppressor Function Vinay Mandati
The role of the C-terminus Merlin in its tumor suppressor function Vinay Mandati To cite this version: Vinay Mandati. The role of the C-terminus Merlin in its tumor suppressor function. Agricultural sciences. Université Paris Sud - Paris XI, 2013. English. NNT : 2013PA112140. tel-01124131 HAL Id: tel-01124131 https://tel.archives-ouvertes.fr/tel-01124131 Submitted on 19 Mar 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 TABLE OF CONTENTS Abbreviations ……………………………………………………………………………...... 8 Resume …………………………………………………………………………………… 10 Abstract …………………………………………………………………………………….. 11 1. Introduction ………………………………………………………………………………12 1.1 Neurofibromatoses ……………………………………………………………………….14 1.2 NF2 disease ………………………………………………………………………………15 1.3 The NF2 gene …………………………………………………………………………….17 1.4 Mutational spectrum of NF2 gene ………………………………………………………..18 1.5 NF2 in other cancers ……………………………………………………………………...20 2. ERM proteins and Merlin ……………………………………………………………….21 2.1 ERMs ……………………………………………………………………………………..21 2.1.1 Band 4.1 Proteins and ERMs …………………………………………………………...21 2.1.2 ERMs structure ………………………………………………………………………....23 2.1.3 Sub-cellular localization and tissue distribution of ERMs ……………………………..25 2.1.4 ERM proteins and their binding partners ……………………………………………….25 2.1.5 Assimilation of ERMs into signaling pathways ………………………………………...26 2.1.5. A. ERMs and Ras signaling …………………………………………………...26 2.1.5. B. ERMs in membrane transport ………………………………………………29 2.1.6 ERM functions in metastasis …………………………………………………………...30 2.1.7 Regulation of ERM proteins activity …………………………………………………...31 2.1.7. -
Fas Role in Ischemic Stroke; Not Only in Apoptosis
a ular nd G ec en l e o t i M c f M Sergeeva et al., J Mol Genet Med 2016, 10:4 o l e d Journal of Molecular and Genetic a i n c r DOI: 10.4172/1747-0862.1000236 i n u e o J ISSN: 1747-0862 Medicine ReviewResearch Article Article Open Access Fas Role in Ischemic Stroke: Not Only in Apoptosis Sergeeva SP1, Gorbacheva LR2,3*, Breslavich ID4 and Cherdak MA5 1Department of Pathophysiology, I.M Sechenov First Moscow State Medical University, Trubetskaya Street, 8-2, Moscow, Russia 2Department of Physiology, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, Moscow, Russia 3Department of Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, Moscow, Russia 4Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, GSP-1, 1 Leninskiye Gory, 1, Moscow, Russia 5Department of Neurological Diseases, I.M. Sechenov First Moscow State Medical University, Trubetskaya street, Moscow, Russia Abstract The receptors, whose ligand interaction activation was previously considered to be associated with initiation of apoptosis only, can have a range of biological effects: apoptosis, inflammation, proliferation, and differentiation. Therefore, interaction between death receptor and its ligand does not always mean the initiation of programmed cell death and blocking of this ligand-receptor interaction can affect the initiation of recovery and neuroplasticity mechanisms. Fas is one of these death receptors. The following review represents data on the conditions of Fas- dependent signal pathways induction in ischemic stroke. There is a possibility for the development of new target neuroprotective drugs with selective effects on different separated signal pathways, activated by ligand-receptor interactions in Fas-FasL (Fas ligand) system. -
ERM Protein Family
Cell Biology 2018; 6(2): 20-32 http://www.sciencepublishinggroup.com/j/cb doi: 10.11648/j.cb.20180602.11 ISSN: 2330-0175 (Print); ISSN: 2330-0183 (Online) Structure and Functions: ERM Protein Family Divine Mensah Sedzro 1, †, Sm Faysal Bellah 1, 2, †, *, Hameed Akbar 1, Sardar Mohammad Saker Billah 3 1Laboratory of Cellular Dynamics, School of Life Science, University of Science and Technology of China, Hefei, China 2Department of Pharmacy, Manarat International University, Dhaka, Bangladesh 3Department of Chemistry, Govt. M. M. University College, Jessore, Bangladesh Email address: *Corresponding author † These authors contributed equally to this work To cite this article: Divine Mensah Sedzro, Sm Faysal Bellah, Hameed Akbar, Sardar Mohammad Saker Billah. Structure and Functions: ERM Protein Family. Cell Biology . Vol. 6, No. 2, 2018, pp. 20-32. doi: 10.11648/j.cb.20180602.11 Received : September 15, 2018; Accepted : October 6, 2018; Published : October 29, 2018 Abstract: Preservation of the structural integrity of the cell depends on the plasma membrane in eukaryotic cells. Interaction between plasma membrane, cytoskeleton and proper anchorage influence regular cellular processes. The needed regulated connection between the membrane and the underlying actin cytoskeleton is therefore made available by the ERM (Ezrin, Radixin, and Moesin) family of proteins. ERM proteins also afford the required environment for the diffusion of signals in reactions to extracellular signals. Other studies have confirmed the importance of ERM proteins in different mode organisms and in cultured cells to emphasize the generation and maintenance of specific domains of the plasma membrane. An essential attribute of almost all cells are the specialized membrane domains. -
Ezrin Intracellular Cytoskeleton Marker Is Over Expressed in Pancreatic Ductal Adenocarcinoma: a Prospective Cohort Study
Research Article Clinics in Oncology Published: 01 Mar, 2021 Ezrin Intracellular Cytoskeleton Marker is Over Expressed in Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study Livia Petrusel1, Ioana Rusu2, Ramona Suharoschi3, Andrada Seicean1, Daniel Corneliu Leucuta4* and Radu Seicean5 1Department of Gastroenterology, Iuliu Hatieganu University of Medicine and Pharmacy, Romania 2Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy, Romania 3Department of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Romania 4Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, Romania 5First Surgery Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Romania Abstract Background: Intracellular cytoskeleton in Pancreatic Ductal Adenocarcinoma (PDAC) might be a key factor in its poor outcome. Reliable biomarkers estimating the cytoskeleton involvement are lacking. Ezrin is involved in intracellular signaling and adhesion, by linking in the PI3K/Akt pathways. Aim of the Study: To assess the significance of ezrin protein expression in PDAC related to the clinical stage and survival. Methods: This prospective cohort study enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies. The plasma levels of ezrin were analyzed using western blotting and were correlated with the clinicopathological features and survival data. These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the OPEN ACCESS patients included in the study and a supplementary group of surgically resected specimens from *Correspondence: patients with a benign disease. Daniel Corneliu Leucuta, Department Results: The study comprised 51 patients with PDAC, 53 controls and a supplementary group of of Medical Informatics and Biostatistics, 13 normal pancreatic tissue samples. -
Molecular Biology of the Cell Et Al., 2007)
MBoC | ARTICLE CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation J. L. Cannona,*, P. D. Modya, K. M. Blainea, E. J. Chenb, A. D. Nelsona, L. J. Saylesa, T. V. Moorec, B. S. Claya, N. O. Dulina, R. A. Shillinga,c, J. K. Burkhardtb, and A. I. Sperlinga,c aSection of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637; bDepartment of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104; cCommittee on Immunology, University of Chicago, Chicago, IL 60637 ABSTRACT Cell polarization is a key feature of cell motility, driving cell migration to tissues. Monitoring Editor CD43 is an abundantly expressed molecule on the T-cell surface that shows distinct localiza- Josephine Clare Adams tion to the migrating T-cell uropod and the distal pole complex (DPC) opposite the immuno- University of Bristol logical synapse via association with the ezrin-radixin-moesin (ERM) family of actin regulatory Received: Jul 13, 2010 proteins. CD43 regulates multiple T-cell functions, including T-cell activation, proliferation, Revised: Jan 7, 2011 apoptosis, and migration. We recently demonstrated that CD43 regulates T-cell trafficking Accepted: Jan 19, 2011 through a phosphorylation site at Ser-76 (S76) within its cytoplasmic tail. Using a phosphory- lation-specific antibody, we now find that CD43 phosphorylation at S76 is enhanced by mi- gration signals. We further show that CD43 phosphorylation and normal T-cell trafficking depend on CD43 association with ERM proteins. Interestingly, mutation of S76 to mimic phosphorylation enhances T-cell migration and CD43 movement to the DPC while blocking ERM association, showing that CD43 movement can occur in the absence of ERM binding.