IGF2BP1 Is a Targetable SRC/MAPK-Dependent Driver Of
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IGF2BP1 (D-9): Sc-166344
SANTA CRUZ BIOTECHNOLOGY, INC. IGF2BP1 (D-9): sc-166344 BACKGROUND STORAGE Insulin like growth factor 2 mRNA binding proteins (IGF2BPs) bind RNA and Store at 4° C, **DO NOT FREEZE**. Stable for one year from the date of influence RNA synthesis and metabolism. IGF2BP1, also known as coding shipment. Non-hazardous. No MSDS required. region determinant-binding protein/Insulin-like growth factor II mRNA-binding protein (CRD-BP), IMP1 or VICKZ1; IGF2BP2 (IMP2, VICKZ2, p62); and IGF2BP2 DATA (IMP3, KOC1, VICKZ3) contain a unique combination of RNA recognition motifs A B and four hnRNP K homology domains. IGF2BP1 is abundant in embryonal ABC DEF tissues and is expressed in 81% of colon cancers, 73% of sarcomas and 132 K – 58.5% of breast cancers. It recognizes c-Myc, IGF-II and t mRNAs, and H19 90 K – RNA, and plays a major role in proliferation of K-562 cells by an IGF-II-depen- 55 K – IGF2BP1 dent mechanism. IGF2BP2 binds the 5' UTR of IGF-II mRNA and influences tumor cell growth, in which IGF2BP2 is associated with apoptosis induced 43 K – by tretinoin. IGF2BP3 knockdown by RNA interference decreases levels of IGF-II protein without affecting IGF-II, c-Myc, or b Actin mRNA and H19 RNA levels. IGF2BP3 is a marker for carcinomas and high-grade dysplastic lesions IGF2BP1 (D-9): sc-166344. Western blot analysis IGF2BP1 (D-9): sc-166344. Immunofluorescence staining ofIGF2BP1 expressioninHEK293 (A), NIH/3T3 (B), of methanol-fixed HeLa cells showing nucleolar and of pancreatic ductal epithelium. K-562 (C), U-698-M (D) and Raji (E)wholecell lysates cytoplasmic localization (A). -
Exome Sequencing Revealed DNA Variants in NCOR1, IGF2BP1, SGLT2 and NEK11 As Potential Novel Causes of Ketotic Hypoglycemia in C
www.nature.com/scientificreports OPEN Exome sequencing revealed DNA variants in NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of ketotic hypoglycemia in children Yazeid Alhaidan1,2,3,4*, Martin J. Larsen 1,2, Anders Jørgen Schou5, Maria H. Stenlid6, Mohammed A. Al Balwi 3,4, Henrik Thybo Christesen2,5,7,9 & Klaus Brusgaard1,2,8,9 Unexplained or idiopathic ketotic hypoglycemia (KH) is the most common type of hypoglycemia in children. The diagnosis is based on the exclusion of routine hormonal and metabolic causes of hypoglycemia. We aimed to identify novel genes that cause KH, as this may lead to a more targeted treatment. Deep phenotyping of ten preschool age at onset KH patients (boys, n = 5; girls, n = 5) was performed followed by trio exome sequencing and comprehensive bioinformatics analysis. Data analysis revealed four novel candidate genes: (1) NCOR1 in a patient with KH, iron defciency and loose stools; (2) IGF2BP1 in a proband with KH, short stature and delayed bone age; (3) SLC5A2 in a proband with KH, intermittent glucosuria and extremely elevated p-GLP-1; and (4) NEK11 in a proband with ketotic hypoglycemia and liver afiction. These genes are associated with diferent metabolic processes, such as gluconeogenesis, translational regulation, and glucose transport. In conclusion, WES identifed DNA variants in four diferent genes as potential novel causes of IKH, suggesting that IKH is a heterogeneous disorder that can be split into several novel diseases: NCOR1-KH, IGF2BP1-KH, SGLT2-KH or familial renal glucosuria KH, and NEK11-KH. Precision medicine treatment based on exome sequencing may lead to advances in the management of IKH. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
The M A-Related Gene Signature for Predicting the Prognosis of Breast Cancer
The m6A-related gene signature for predicting the prognosis of breast cancer Shanliang Zhong1,*, Zhenzhong Lin2,*, Huanwen Chen3, Ling Mao4, Jifeng Feng5 and Siying Zhou6 1 Center of Clinical Laboratory Science, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China 2 Department of Pathology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China 3 Xinglin laboratory, The First Affiliated Hospital of Xiamen University, Nanjing, China 4 Department of Thyroid Breast Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China 5 Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China 6 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China * These authors contributed equally to this work. ABSTRACT N6-methyladenosine (m6A) modification has been shown to participate in tumorigen- esis and metastasis of human cancers. The present study aimed to investigate the roles of m6A RNA methylation regulators in breast cancer. We used LASSO regression to identify m6A-related gene signature predicting breast cancer survival with the datasets downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA). RNA-Seq data of 3409 breast cancer patients from GSE96058 and 1097 from TCGA were used in present study. A 10 m6A-related gene signature associated with prognosis was identified from 22 m6A RNA methylation regulators. The signature divided patients into low- and high-risk group. High-risk patients had a worse prognosis than the low-risk group. -
N-Glycan Trimming in the ER and Calnexin/Calreticulin Cycle
Neurotransmitter receptorsGABA and A postsynapticreceptor activation signal transmission Ligand-gated ion channel transport GABAGABA Areceptor receptor alpha-5 alpha-1/beta-1/gamma-2 subunit GABA A receptor alpha-2/beta-2/gamma-2GABA receptor alpha-4 subunit GABAGABA receptor A receptor beta-3 subunitalpha-6/beta-2/gamma-2 GABA-AGABA receptor; A receptor alpha-1/beta-2/gamma-2GABA receptoralpha-3/beta-2/gamma-2 alpha-3 subunit GABA-A GABAreceptor; receptor benzodiazepine alpha-6 subunit site GABA-AGABA-A receptor; receptor; GABA-A anion site channel (alpha1/beta2 interface) GABA-A receptor;GABA alpha-6/beta-3/gamma-2 receptor beta-2 subunit GABAGABA receptorGABA-A receptor alpha-2receptor; alpha-1 subunit agonist subunit GABA site Serotonin 3a (5-HT3a) receptor GABA receptorGABA-C rho-1 subunitreceptor GlycineSerotonin receptor subunit3 (5-HT3) alpha-1 receptor GABA receptor rho-2 subunit GlycineGlycine receptor receptor subunit subunit alpha-2 alpha-3 Ca2+ activated K+ channels Metabolism of ingested SeMet, Sec, MeSec into H2Se SmallIntermediateSmall conductance conductance conductance calcium-activated calcium-activated calcium-activated potassium potassium potassiumchannel channel protein channel protein 2 protein 1 4 Small conductance calcium-activatedCalcium-activated potassium potassium channel alpha/beta channel 1 protein 3 Calcium-activated potassiumHistamine channel subunit alpha-1 N-methyltransferase Neuraminidase Pyrimidine biosynthesis Nicotinamide N-methyltransferase Adenosylhomocysteinase PolymerasePolymeraseHistidine basic -
YAP and TAZ Mediators at the Crossroad Between Metabolic and Cellular Reprogramming
H OH metabolites OH Review YAP and TAZ Mediators at the Crossroad between Metabolic and Cellular Reprogramming Giorgia Di Benedetto, Silvia Parisi , Tommaso Russo and Fabiana Passaro * Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 40, 80138 Napoli, Italy; [email protected] (G.D.B.); [email protected] (S.P.); [email protected] (T.R.) * Correspondence: [email protected] Abstract: Cell reprogramming can either refer to a direct conversion of a specialized cell into another or to a reversal of a somatic cell into an induced pluripotent stem cell (iPSC). It implies a peculiar modification of the epigenetic asset and gene regulatory networks needed for a new cell, to better fit the new phenotype of the incoming cell type. Cellular reprogramming also implies a metabolic rearrangement, similar to that observed upon tumorigenesis, with a transition from oxidative phosphorylation to aerobic glycolysis. The induction of a reprogramming process requires a nexus of signaling pathways, mixing a range of local and systemic information, and accumulating evidence points to the crucial role exerted by the Hippo pathway components Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ). In this review, we will first provide a synopsis of the Hippo pathway and its function during reprogramming and tissue regeneration, then we introduce the latest knowledge on the interplay between YAP/TAZ Citation: Di Benedetto, G.; Parisi, S.; and metabolism and, finally, we discuss the possible role of YAP/TAZ in the orchestration of the Russo, T.; Passaro, F. YAP and TAZ metabolic switch upon cellular reprogramming. -
Proteomic Profiling of Retinoblastoma by High Resolution Mass Spectrometry Ravikanth Danda1,5, Kalaivani Ganapathy1, Gajanan Sathe4, Anil K
Danda et al. Clin Proteom (2016) 13:29 DOI 10.1186/s12014-016-9128-7 Clinical Proteomics RESEARCH Open Access Proteomic profiling of retinoblastoma by high resolution mass spectrometry Ravikanth Danda1,5, Kalaivani Ganapathy1, Gajanan Sathe4, Anil K. Madugundu4, Sharavan Ramachandran1, Uma Maheswari Krishnan5, Vikas Khetan3, Pukhraj Rishi3, T. S. Keshava Prasad4, Akhilesh Pandey6,7,8,9, Subramanian Krishnakumar1*, Harsha Gowda4* and Sailaja V. Elchuri2* Abstract Background: Retinoblastoma is an ocular neoplastic cancer caused primarily due to the mutation/deletion of RB1 gene. Due to the rarity of the disease very limited information is available on molecular changes in primary retino- blastoma. High throughput analysis of retinoblastoma transcriptome is available however the proteomic landscape of retinoblastoma remains unexplored. In the present study we used high resolution mass spectrometry-based quantita- tive proteomics to identify proteins associated with pathogenesis of retinoblastoma. Methods: We used five pooled normal retina and five pooled retinoblastoma tissues to prepare tissue lysates. Equivalent amount of proteins from each group was trypsin digested and labeled with iTRAQ tags. The samples were analyzed on Orbitrap Velos mass spectrometer. We further validated few of the differentially expressed proteins by immunohistochemistry on primary tumors. Results: We identified and quantified a total of 3587 proteins in retinoblastoma when compared with normal adult retina. In total, we identified 899 proteins that were differentially expressed in retinoblastoma with a fold change of 2 of which 402 proteins were upregulated and 497 were down regulated. Insulin growth factor 2 mRNA binding protein≥ 1 (IGF2BP1), chromogranin A, fetuin A (ASHG), Rac GTPase-activating protein 1 and midkine that were found to be overexpressed in retinoblastoma were further confirmed by immunohistochemistry by staining 15 independent retinoblastoma tissue sections. -
A Novel Hypoxic Long Noncoding RNA KB-1980E6.3 Maintains Breast Cancer Stem Cell Stemness Via Interacting with IGF2BP1 to Facilitate C-Myc Mrna Stability
Oncogene (2021) 40:1609–1627 https://doi.org/10.1038/s41388-020-01638-9 ARTICLE A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability 1 2 3 4 1 1 1 1 1 Pengpeng Zhu ● Fang He ● Yixuan Hou ● Gang Tu ● Qiao Li ● Ting Jin ● Huan Zeng ● Yilu Qin ● Xueying Wan ● 1 1 5 1 Yina Qiao ● Yuxiang Qiu ● Yong Teng ● Manran Liu Received: 15 June 2020 / Revised: 13 November 2020 / Accepted: 18 December 2020 / Published online: 19 January 2021 © The Author(s), under exclusive licence to Springer Nature Limited 2021. This article is published with open access Abstract The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB- 1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both 1234567890();,: 1234567890();,: in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/ IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors. -
Novel Regulators of the IGF System in Cancer
biomolecules Review Novel Regulators of the IGF System in Cancer Caterina Mancarella 1, Andrea Morrione 2 and Katia Scotlandi 1,* 1 IRCCS Istituto Ortopedico Rizzoli, Laboratory of Experimental Oncology, 40136 Bologna, Italy; [email protected] 2 Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA; [email protected] * Correspondence: [email protected]; Tel.: +39-051-6366-760 Abstract: The insulin-like growth factor (IGF) system is a dynamic network of proteins, which includes cognate ligands, membrane receptors, ligand binding proteins and functional downstream effectors. It plays a critical role in regulating several important physiological processes including cell growth, metabolism and differentiation. Importantly, alterations in expression levels or activa- tion of components of the IGF network are implicated in many pathological conditions including diabetes, obesity and cancer initiation and progression. In this review we will initially cover some general aspects of IGF action and regulation in cancer and then focus in particular on the role of transcriptional regulators and novel interacting proteins, which functionally contribute in fine tuning IGF1R signaling in several cancer models. A deeper understanding of the biological relevance of this network of IGF1R modulators might provide novel therapeutic opportunities to block this system in neoplasia. Keywords: IGF system; cancer; transcriptional regulators; functional regulation; circular RNAs; IGF2BPs; ADAR; DDR1; E-cadherin; decorin Citation: Mancarella, C.; Morrione, A.; Scotlandi, K. Novel Regulators of the IGF System in Cancer. 1. Introduction Biomolecules 2021, 11, 273. https:// doi.org/10.3390/biom11020273 The insulin-like growth factor (IGF) system is a network of ligands, binding proteins and receptors regulating crucial physiological and pathological biological processes. -
MAPK4 Overexpression Promotes Tumor Progression Via Noncanonical Activation of AKT/Mtor Signaling
The Journal of Clinical Investigation RESEARCH ARTICLE MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling Wei Wang,1 Tao Shen,1 Bingning Dong,1 Chad J. Creighton,2,3 Yanling Meng,1 Wolong Zhou,1 Qing Shi,1 Hao Zhou,1 Yinjie Zhang,1 David D. Moore,1 and Feng Yang1 1Department of Molecular and Cellular Biology, 2Department of Medicine, and 3Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA. MAPK4 is an atypical MAPK. Currently, little is known about its physiological function and involvement in diseases, including cancer. A comprehensive analysis of 8887 gene expression profiles in The Cancer Genome Atlas (TCGA) revealed that MAPK4 overexpression correlates with decreased overall survival, with particularly marked survival effects in patients with lung adenocarcinoma, bladder cancer, low-grade glioma, and thyroid carcinoma. Interestingly, human tumor MAPK4 overexpression also correlated with phosphorylation of AKT, 4E-BP1, and p70S6K, independent of the loss of PTEN or mutation of PIK3CA. This led us to examine whether MAPK4 activates the key metabolic, prosurvival, and proliferative kinase AKT and mTORC1 signaling, independent of the canonical PI3K pathway. We found that MAPK4 activated AKT via a novel, concerted mechanism independent of PI3K. Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308. It also activated mTORC2 to phosphorylate AKT at serine 473 for full activation. MAPK4 overexpression induced oncogenic outcomes, including transforming prostate epithelial cells into anchorage-independent growth, and MAPK4 knockdown inhibited cancer cell proliferation, anchorage-independent growth, and xenograft growth. We concluded that MAPK4 can promote cancer by activating the AKT/mTOR signaling pathway and that targeting MAPK4 may provide a novel therapeutic approach for cancer. -
The Devil Is in the Domain: Understanding Protein Recognition of Multiple RNA Targets
The devil is in the domain: understanding protein recognition of multiple RNA targets Glen R. Gronland1 and Andres Ramos1 1. Institute of Structural and Molecular Biology, University College London, London WC1E 6XA, UK Correspondence to Andres Ramos: [email protected] Abstract: RNA regulation provides a finely-tuned and highly-coordinated control of gene expression. Regulation is mediated by hundreds to thousands of multi-functional RNA-binding proteins which often interact with large sets of RNAs. In this brief review, we focus on recent work that highlights how the proteins use multiple RNA-binding domains to interact selectively with the different RNA targets. De-convoluting the molecular complexity of the RNA regulatory network is essential to understanding cell differentiation and function, and requires accurate models for protein-RNA recognition and protein target selectivity. We discuss that the structural and molecular understanding of the key determinant of recognition, together with the availability of methods to examine protein-RNA interactions at the transcriptome level, may provide an avenue to establish these models. Abbreviations list: CSD, Cold shock domain dsRBD, Double-stranded RNA-binding domain KH, hnRNP K-homology mRNA, Messenger RNA ncRNA, Non-coding RNA RBD, RNA-binding domain RBP, RNA-binding protein RRM, RNA-recognition motif ZnF, Zinc finger Introduction The combined regulation of the various steps in the metabolism and transport of messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) multiplies genomic potential, and allows cellular differentiation and the development of complex organisms. In the cell, functional RNAs are associated with a fluctuating assortment of multi-domain RNA-binding proteins (RBPs), forming integrated complexes, whose composition directs the fate of the transcript1,2. -
Zipcode Binding Protein 1 (ZBP1; IGF2BP1): a Model for Sequence-Specific RNA Regulation
Zipcode Binding Protein 1 (ZBP1; IGF2BP1): A Model for Sequence-Specific RNA Regulation 1 1,5 1,5 1,2 JEETAYU BISWAS, LETI NUNEZ, SULAGNA DAS, YOUNG J. YOON, 1,3 1,2,4 CAROLINA ELISCOVICH, AND ROBERT H. SINGER 1Department of Anatomy and Structural Biology, 2Department of Neuroscience, 3Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA 4Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, Virginia 20147, USA Correspondence: [email protected] The fate of an RNA, from its localization, translation, and ultimate decay, is dictated by interactions with RNA binding proteins (RBPs). β-actin mRNA has functioned as the classic example of RNA localization in eukaryotic cells. Studies of β-actin mRNA over the past three decades have allowed understanding of how RBPs, such as ZBP1 (IGF2BP1), can control both RNA localization and translational status. Here, we summarize studies of β-actin mRNA and focus on how ZBP1 serves as a model for understanding interactions between RNA and their binding protein(s). Central to the study of RNA and RBPs were technological developments that occurred along the way. We conclude with a future outlook highlighting new technologies that may be used to address still unanswered questions about RBP-mediated regulation of mRNA during its life cycle, within the cell. Changes in protein synthesis define all aspects of a RNAs tested (actin, vimentin, and tubulin), actin had cell’s life. Although most cells carry identical copy num- the most distinct localization pattern. Approximately bers of their DNA, differences in transcription and trans- 95% of myoblasts had a nonrandom distribution of β-actin lation define both cellular fate and moment to moment mRNA, in which RNAs were concentrated at the cell cellular decisions.