Article
Multidisciplinary Sciences
Robert F. Hennigan, Craig S. Thomson, Kye Stachowski, Nicolas Nassar, Nancy Ratner
Summary: Neurofibromatosis Type 2 is a genetic disease characterized by nerve tumors. Merlin, encoded by the NF2 gene, has a role in tumor suppressor activity. It was found that Merlin dimerizes through a FERM-FERM interaction. Dimerization controls interactions with specific binding partners and occurs after a transition from closed to open conformation.
Article
Oncology
Emmanuel A. Maze, Bora Agit, Shona Reeves, David A. Hilton, David B. Parkinson, Liyam Laraba, Emanuela Ercolano, Kathreena M. Kurian, C. Oliver Hanemann, Robert D. Belshaw, Sylwia Ammoun
Summary: Deficiency of the tumor suppressor Merlin leads to the development of schwannoma and meningioma tumors. This study identifies the endogenous retrovirus HERV-K as a critical regulator in these tumors and suggests potential therapeutic strategies using retroviral protease inhibitors and TEAD inhibitors.
Article
Dermatology
Verena Staedtke, Piotr Topilko, Lu Q. Le, Kevin Grimes, David A. Largaespada, Ross L. Cagan, Matthew R. Steensma, Anat Stemmer-Rachamimov, Jaishri O. Blakeley, Steven D. Rhodes, Ina Ly, Carlos G. Romo, Sang Y. Lee, Eduard Serra
Summary: Neurofibromatosis type 1 (NF1) is caused by a nonfunctional NF1 tumor suppressor gene, resulting in the development of cutaneous neurofibromas (cNFs). Incomplete understanding of cNF pathophysiology and limitations in experimental modeling have hindered the development of cNF treatment. Recent advances in preclinical in vitro and in vivo modeling provide unprecedented opportunities for therapeutic discovery and improving our understanding of cNF biology.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Yi-Hui Gu, Xi-Wei Cui, Jie-Yi Ren, Man-Mei Long, Wei Wang, Cheng-Jiang Wei, Rehanguli Aimaier, Yue-Hua Li, Man-Hon Chung, Bin Gu, Qing-Feng Li, Zhi-Chao Wang
Summary: This study identified optimal reference genes for relative quantitative analysis in NF1 related cell lines, recommending the combinational use of PPIA and TBP in malignant Schwann cell lines, and the use of single reference genes PPIA or PRLP0 in benign Schwann cell lines to improve the accuracy and reproducibility of RT-qPCR analyses.
Article
Biochemistry & Molecular Biology
Yosuke Senju, Emi Hibino
Summary: Neurofibromatosis type 2 (NF2), caused by the mutated merlin gene, belongs to the FERM domain-containing 4.1 superfamily. Merlin, a tumor suppressor, shares sequence homology with ERM proteins and plays important roles in cell-cell adhesions. This article provides insights into the molecular functions of merlin and its interactions with PI(4,5)P2, shedding light on its fundamental roles in cells and tissues.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Review
Biochemistry & Molecular Biology
Maximilian Scheer, Sandra Leisz, Eberhard Sorge, Olha Storozhuk, Julian Prell, Ivy Ho, Anja Harder
Summary: NF1 gene mutations are found in various tumors, and loss of NF1 function plays a crucial role in inducing the aggressive MES subtype in glioblastoma. This process is mediated through the NF1-MAPK-FOSL1 axis and may offer novel therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Ling-Ling Ge, Ming-Yan Xing, Hai-Bing Zhang, Zhi-Chao Wang
Summary: This review summarizes the accumulating evidence on the cellular and molecular pathogenesis of neurofibroma development. Neurofibromatosis type 1 (NF1) is a genetic tumor predisposition syndrome that affects about 1 in 3000 newborns and is caused by mutations in the NF1 gene. The distinct characteristics of plexiform and cutaneous neurofibromas have prompted hypotheses about the origin and developmental features of these tumors.
Article
Chemistry, Medicinal
Yanru Ji, Ying Fang, Jianhua Wu
Summary: This study reveals the mechanism of how Talin and Kindlin synergistically activate integrin. By simulating the process of mechanosignaling, it is found that mild stretching enhances the binding of integrin to Talin, thereby promoting integrin activation and the formation of a stable complex.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Mathematics
Lijia Ding
Summary: In this paper, singular integral operators induced by the Bergman kernel and Szego kernel are investigated on irreducible bounded symmetric domains. The authors completely characterize when these operators belong to Schatten class operator ideals using analytic numerical invariants of the domains. Additionally, two trace formulae and a new integral estimate related to the Forelli-Rudin estimate are obtained.
ADVANCES IN MATHEMATICS
(2022)
Article
Biochemistry & Molecular Biology
Brandon Havranek, Shahidul M. Islam
Summary: The majority of disease-causing genetic variations in the human genome are due to non-synonymous single nucleotide polymorphisms (nsSNPs). This study focused on investigating the pathogenic effect of 14 nsSNPs in the merlin FERM domain, identifying G197C and L234R mutations as deleterious mutations associated with mild and severe forms of NF2. Molecular dynamics simulations showed that mutant structures were more flexible than the wildtype, with the L234R mutation exhibiting greater structural instability, potentially impacting merlin's ability to regulate the Hippo signaling pathway.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Multidisciplinary Sciences
Cordelia Rauskolb, Ahri D. Han, Elmira Kirichenko, Consuelo Ibar, Kenneth Irvine
Summary: This study reveals that the Ajuba LIM protein Jub regulates Hippo signaling through cytoskeletal tension by interacting with the kinase Warts, and participates in feedback regulation of junctional tension through regulation of the cytohesin Steppke. The different LIM domains of Jub have distinct functions in interaction with its partners and regulation of cellular processes.
Article
Surgery
Chengrui Guo, Lucia Zhou, Yi Sun, Xiaojie Hu
Summary: In this study, the authors presented two cases of neurofibroma patients and used cell culture and genetic sequencing experiments to identify NF1 mutation in neurofibroma Schwann cells, providing an accurate diagnosis of solitary neurofibroma and highlighting its importance in fertility consultation.
JOURNAL OF CRANIOFACIAL SURGERY
(2022)
Article
Biochemistry & Molecular Biology
Muhammad Ali, Alisa Khramushin, Vikash K. Yadav, Ora Schueler-Furman, Ylva Ivarsson
Summary: The ERM family proteins and merlin participate in scaffolding and signaling events at the cell cortex. By screening the FERM domains of these proteins against a phage library, they discovered novel interaction motifs and binding sites. They defined distinct binding sites and provided a molecular understanding of how peptides with distinct motifs bind to different sites on the moesin FERM phosphotyrosine binding-like subdomain.
Article
Mathematics, Applied
William Alexandre
Summary: We prove the existence of a solution to the H-p-corona problem for two generators in convex domains of finite type in C-n, where n is greater than or equal to 2.
JOURNAL OF MATHEMATICAL ANALYSIS AND APPLICATIONS
(2022)
Article
Mathematics
Qi Sun, Ciqiang Zhuo
Summary: In this article, the authors demonstrate that the operator extending from the variable Triebel-Lizorkin-type space on domain Omega to the corresponding space on R-n via the Peetre maximal function and following the approach of Rychkov. This extension is based on the establishment of extension results for the classical Triebel-Lizorkin spaces and Besov spaces.
BULLETIN OF THE MALAYSIAN MATHEMATICAL SCIENCES SOCIETY
(2022)
Article
Oncology
Irene Paganini, Gabriele Lorenzo Capone, Jeremie Vitte, Roberta Sestini, Anna Laura Putignano, Marco Giovannini, Laura Papi
JOURNAL OF NEURO-ONCOLOGY
(2018)
Article
Genetics & Heredity
Michael J. Fisher, Allan J. Belzberg, Peter de Blank, Thomas De Raedt, Florent Elefteriou, Rosalie E. Ferner, Marco Giovannini, Gordon J. Harris, Michel Kalamarides, Matthias A. Karajannis, AeRang Kim, Conxi Lazaro, Lu Q. Le, Wei Li, Robert Listernick, Staci Martin, Helen Morrison, Eric Pasmant, Nancy Ratner, Elisabeth Schorry, Nicole J. Ullrich, David Viskochil, Brian Weiss, Brigitte C. Widemann, Yuan Zhu, Annette Bakker, Eduard Serra
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2018)
Article
Oncology
Marisa A. Fuse, Christine T. Dinh, Jeremie Vitte, Joanna Kirkpatrick, Thomas Mindos, Stephani Klingeman Plati, Juan I. Young, Jie Huang, Annemarie Carlstedt, Maria Clara Franco, Konstantin Brnjos, Jackson Nagamoto, Alejandra M. Petrilli, Alicja J. Copik, Julia N. Soulakova, Olena Bracho, Denise Yan, Rahul Mittal, Rulong Shen, Fred F. Telischi, Helen Morrison, Marco Giovannini, Xue-Zhong Liu, Long-Sheng Chang, Cristina Fernandez-Valle
Article
Genetics & Heredity
Rosalie E. Ferner, Annette Bakker, Ype Elgersma, D. Gareth R. Evans, Marco Giovannini, Eric Legius, Alison Lloyd, Ludwine M. Messiaen, Scott Plotkin, Karlyne M. Reilly, Aaron Schindeler, Miriam J. Smith, Nicole J. Ullrich, Brigitte Widemann, Larry S. Sherman
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2019)
Article
Clinical Neurology
Daniel S. Roberts, Rahul Maurya, Yuka Takemon, Jeremie Vitte, Liang Gong, Juanjuan Zhao, Chee-Hong Wong, William Slattery, Kevin A. Peng, Gregory Lekovic, Marc S. Schwartz, Ketan Bulsara, Chew Yee Ngan, Marco Giovannini, Chia-Lin Wei
OTOLOGY & NEUROTOLOGY
(2019)
Article
Oncology
Sherif G. Ahmed, Ahmed Abdelnabi, Casey A. Maguire, Mohamed Doha, Jessica E. Sagers, Rebecca M. Lewis, Alona Muzikansky, Marco Giovannini, Anat Stemmer-Rachamimov, Konstantina M. Stankovic, Giulia Fulci, Gary J. Brenner
Article
Biochemistry & Molecular Biology
Vinay Mandati, Laurence Del Maestro, Florent Dingli, Berangere Lombard, Damarys Loew, Nicolas Molinie, Stephane Romero, Daniel Bouvard, Daniel Louvard, Alexis M. Gautreau, Eric Pasmant, Dominique Lallemand
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Oncology
Junzhi Ma, Janina Klemm, Monserrat Gerardo-Ramirez, Lucien Frappart, Darko Castven, Diana Becker, Ansgar Zoch, Romain Parent, Birke Bartosch, Kerstin Minnich, Marco Giovannini, Sven Danckwardt, Nils Hartmann, Helen Morrison, Peter Herrlich, Jens U. Marquardt, Monika Hartmann
INTERNATIONAL JOURNAL OF CANCER
(2020)
Article
Biochemistry & Molecular Biology
Marc R. Block, Molly Brunner, Theo Ziegelmeyer, Dominique Lallemand, Mylene Pezet, Genevieve Chevalier, Philippe Ronde, Cecile Gauthier-Rouviere, Bernhard Wehrle-Haller, Daniel Bouvard
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Genetics & Heredity
Eric Legius, Ludwine Messiaen, Pierre Wolkenstein, Patrice Pancza, Robert A. Avery, Yemima Berman, Jaishri Blakeley, Dusica Babovic-Vuksanovic, Karin Soares Cunha, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, David H. Gutmann, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Sirkku Peltonen, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Anat Stemmer-Rachamimov, David A. Stevenson, Gianluca Tadini, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, D. Gareth Evans, Scott R. Plotkin
Summary: The study revised the diagnostic criteria for neurofibromatosis type 1 (NF1) and established criteria for Legius syndrome (LGSS) by combining major developments in genetics, ophthalmology, dermatology, and neuroimaging. Consensus on minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS was reached, with recommendations for mosaic forms of these conditions. Continued refinement of these new criteria will be necessary to study their diagnostic properties, reconsider criteria not included, and identify new features of the conditions, hence proposing an initiative to periodically update the diagnostic criteria for NF1 and LGSS.
GENETICS IN MEDICINE
(2021)
Article
Cell Biology
Mohamed Ishan, Guiqian Chen, Wenxin Yu, Zhonghou Wang, Marco Giovannini, Xinwei Cao, Hong-Xiang Liu
Summary: The study aimed to understand the roles of tumor suppressor Neurofibromin 2 (Nf2) in neural crest (NC)-derived tongue mesenchyme in regulating Hippo signaling and cell proliferation for proper tongue development. The results showed specific alterations in Hippo signaling activity and cell proliferation in Nf2(cKO) mutants, leading to abnormalities in tongue shape and size at different developmental stages.
CELL PROLIFERATION
(2021)
Article
Genetics & Heredity
Scott R. Plotkin, Ludwine Messiaen, Eric Legius, Patrice Pancza, Robert A. Avery, Jaishri O. Blakeley, Dusica Babovic-Vuksanovic, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, Marco Giovannini, David H. Gutmann, Clemens Oliver Hanemann, Michel Kalamarides, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Mia MacCollin, Laura Papi, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Miriam J. Smith, Anat Stemmer-Rachamimov, David A. Stevenson, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, Pierre Wolkenstein, D. Gareth Evans
Summary: The study aims to update the diagnostic criteria for neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. The updated criteria include clinical features and genetic testing, emphasizing the phenotypic overlap between the two conditions.
GENETICS IN MEDICINE
(2022)
Article
Medicine, Research & Experimental
Shilpa Prabhakar, Roberta L. Beauchamp, Pike See Cheah, Akiko Yoshinaga, Edwina Abou Haidar, Sevda Lule, Gayathri Mani, Katia Maalouf, Anat Stemmer-Rachamimov, David H. Jung, Bradley Welling, Marco Giovannini, Scott R. Plotkin, Casey A. Maguire, Vijaya Ramesh, Xandra O. Breakefield
Summary: Loss of function of the NF2 tumor suppressor gene leads to the formation of certain types of tumors. This study demonstrates that introducing merlin back into NF2-null schwannomas through gene replacement can cause tumor regression. In a mouse model, injection of AAV1-merlin resulted in decreased tumor size, reduced cell division, and increased apoptosis.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
Christine Chiasson-MacKenzie, Jeremie Vitte, Ching-Hui Liu, Emily A. Wright, Elizabeth A. Flynn, Shannon L. Stott, Marco Giovannini, Andrea I. McClatchey
Summary: Schwannomas are common tumors that develop on cranial and spinal nerves and are associated with neurofibromatosis type 2 (NF2). Despite genetic uniformity, schwannomas exhibit clinical and therapeutic heterogeneity. The mechanism behind this heterogeneity in NF2-mutant schwannomas is unknown.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Sara H. Isakson, Anthony E. Rizzardi, Alexander W. Coutts, Daniel F. Carlson, Mark N. Kirstein, James Fisher, Jeremie Vitte, Kyle B. Williams, G. Elizabeth Pluhar, Sonika Dahiya, Brigitte C. Widemann, Eva Dombi, Tilat Rizvi, Nancy Ratner, Ludwine Messiaen, Anat O. Stemmer-Rachamimov, Scott C. Fahrenkrug, David H. Gutmann, Marco Giovannini, Christopher L. Moertel, David A. Largaespada, Adrienne L. Watson
COMMUNICATIONS BIOLOGY
(2018)