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Articles 1 - 22 of 22
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo
Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo
Publications and Research
Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …
Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin
Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin
Publications and Research
Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling. While glycolysis is suppressed by AURKA inhibition, we note an increase in the oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO), which was …
Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis
Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis
Publications and Research
The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH …
Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark
Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark
Publications and Research
The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. …
Two And Three-Dimensional Radiographic Imaging Of Contrast Agents In Heterogeneous Live Cell Media To Understand Contrast-Induced Toxicity, Fahaneda Hassan, Aldona Gjoni, Subhendra Sarkar
Two And Three-Dimensional Radiographic Imaging Of Contrast Agents In Heterogeneous Live Cell Media To Understand Contrast-Induced Toxicity, Fahaneda Hassan, Aldona Gjoni, Subhendra Sarkar
Publications and Research
Radiographic imaging was done using low and high energy radiography equipment. The test hypothesis that macromolecular aggregation changes sample noise in imaging samples for optical imaging methods. Inorganic complexes scatter radiation at the molecular level and may increase the sample noise locally. At high and low photon energies in various x-ray machines, sample and background noise were gathered and compared with those from mammography systems from mammography researchers. The samples with high macromolecular aggregates were prepared using various animal cell compositions and imaged under different conditions that produced different macromolecular dynamics within the samples and thus different image-based sample noise. …
Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin
Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin
Publications and Research
The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days. At the forefront of these developments are the extracellular flux and carbon tracing analyses. Through utilization of these techniques our group made the recent observation that acute and chronic c-MET inhibition drives fatty acid oxidation that in …
Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin
Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin
Publications and Research
The mitochondrial permeability transition pore (MPTP) has resisted molecular identification. The original model of the MPTP that proposed the adenine nucleotide translocator (ANT) as the inner membrane pore-forming component was challenged when mitochondria from Ant1/2 double null mouse liver still had MPTP activity. Because mice express three Ant genes, we reinvestigated whether the ANTs comprise the MPTP. Liver mitochondria from Ant1, Ant2, and Ant4 deficient mice were highly refractory to Ca2+-induced MPTP formation, and when also given cyclosporine A (CsA), the MPTP was completely inhibited. Moreover, liver mitochondria from mice with quadruple deletion of Ant1, Ant2, Ant4, and Ppif (cyclophilin …
Putative Cellular And Molecular Roles Of Zika Virus In Fetal And Pediatric Neuropathologies, Rajendra Ghardbaran, Rajendra Ghardbaran, Latchman Somenarain
Putative Cellular And Molecular Roles Of Zika Virus In Fetal And Pediatric Neuropathologies, Rajendra Ghardbaran, Rajendra Ghardbaran, Latchman Somenarain
Publications and Research
Although the World Health Organization declared an end to the recent Zika virus (ZIKV) outbreak and its association with adverse fetal and pediatric outcome, on November 18, 2016, the virus still remains a severe public health threat. Laboratory experiments thus far supported the suspicions that ZIKV is a teratogenic agent. Evidence indicated that ZIKV infection cripples the host cells' innate immune responses, allowing productive replication and potential dissemination of the virus. In addition, studies suggest potential transplacental passage of the virus and subsequent selective targeting of neural progenitor cells (NPCs). Depletion of NPCs by ZIKV is associated with restricted brain …
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Publications and Research
The TIM23 complex is a hub for translocation of preproteins into or across the mitochondrial inner membrane. This dual sorting mechanism is currently being investigated, and in yeast appears to be regulated by a recently discovered subunit, the Mgr2 protein. Deletion of Mgr2p has been found to delay protein translocation into the matrix and accumulation in the inner membrane. This result and other findings suggested that Mgr2p controls the lateral release of inner membrane proteins harboring a stop-transfer signal that follows an N-terminal amino acid signal. However, the mechanism of lateral release is unknown. Here, we used patch clamp electrophysiology …
Retinal Progenitor Cells Release Extracellular Vesicles Containing Developmental Transcription Factors, Microrna And Membrane Proteins, Jing Zhou, Alberto Benito-Martin, Jason Mighty, Lynne Chang, Shima Ghoroghi, Hao Wu, Madeline Wong, Sara Guariglia, Petr Baranov, Michael Young, Rajendra Ghardbaran, Mark Emerson, Milica Tesic Mark, Henrik Molina, M. Valeria Canto-Solar, Hector Peinado Selgas, Stephen Redenti
Retinal Progenitor Cells Release Extracellular Vesicles Containing Developmental Transcription Factors, Microrna And Membrane Proteins, Jing Zhou, Alberto Benito-Martin, Jason Mighty, Lynne Chang, Shima Ghoroghi, Hao Wu, Madeline Wong, Sara Guariglia, Petr Baranov, Michael Young, Rajendra Ghardbaran, Mark Emerson, Milica Tesic Mark, Henrik Molina, M. Valeria Canto-Solar, Hector Peinado Selgas, Stephen Redenti
Publications and Research
A range of cell types, including embryonic stem cells, neurons and astrocytes have been shown to release extracellular vesicles (EVs) containing molecular cargo. Across cell types, EVs facilitate transfer of mRNA, microRNA and proteins between cells. Here we describe the release kinetics and content of EVs from mouse retinal progenitor cells (mRPCs). Interestingly, mRPC derived EVs contain mRNA, miRNA and proteins associated with multipotency and retinal development. Transcripts enclosed in mRPC EVs, include the transcription factors Pax6, Hes1, and Sox2, a mitotic chromosome stabilizer Ki67, and the neural intermediate filaments Nestin and GFAP. Proteomic analysis of EV content revealed retinogenic …
Cloning And Spatiotemporal Expression Of Xenopus Laevis Apolipoprotein Ci, Jyotsna Sridharan, Tomomi Haremaki, Daniel C. Weinstein
Cloning And Spatiotemporal Expression Of Xenopus Laevis Apolipoprotein Ci, Jyotsna Sridharan, Tomomi Haremaki, Daniel C. Weinstein
Publications and Research
Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI has been implicated in atherosclerosis and Alzheimer’s disease in humans. In this study we report the isolation of Xenopus laevis apoCI and describe the expression pattern of this gene during early development, using reverse transcription polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is enriched in the dorsal ectoderm during gastrulation, and is subsequently expressed in sensory placodes, neural tube and cranial neural crest. These data suggest as yet uncharacterized roles for ApoCI during early vertebrate …
The Microbe Directory: An Annotated, Searchable Inventory Of Microbes’ Characteristics, Heba Shaaban, David A. Westfall, Rawhi Mohammad, David Danko, Daniela Bezdan, Ebrahim Afshinnekoo, Nicola Segata, Christopher E. Mason
The Microbe Directory: An Annotated, Searchable Inventory Of Microbes’ Characteristics, Heba Shaaban, David A. Westfall, Rawhi Mohammad, David Danko, Daniela Bezdan, Ebrahim Afshinnekoo, Nicola Segata, Christopher E. Mason
Publications and Research
The Microbe Directory is a collective research effort to profile and annotate more than 7,500 unique microbial species from the MetaPhlAn2 database that includes bacteria, archaea, viruses, fungi, and protozoa. By collecting and summarizing data on various microbes’ characteristics, the project comprises a database that can be used downstream of large-scale metagenomic taxonomic analyses, allowing one to interpret and explore their taxonomic classifications to have a deeper understanding of the microbial ecosystem they are studying. Such characteristics include, but are not limited to: optimal pH, optimal temperature, Gram stain, biofilm-formation, spore-formation, antimicrobial resistance, and COGEM class risk rating. The database …
Insights Into The Molecular Roles Of Zika Virus In Human Reproductive Complications And Congenital Neuropathologies, Rajendra Ghardbaran, Latchman Somenarain
Insights Into The Molecular Roles Of Zika Virus In Human Reproductive Complications And Congenital Neuropathologies, Rajendra Ghardbaran, Latchman Somenarain
Publications and Research
The recent upsurge in the association of congenital neurological disorders and infection by the Zika virus (ZIKV) has resulted in increased research focus on the biology of this flavivirus. Studies in animal models indicate that ZIKV can breach the placental barrier and selectively infect and deplete neuroprogenitor cells (NPCs) of the developing fetus, resulting in changes of brain structures, reminiscent of human microcephaly. In vitro and ex vivo studies using human cells and tissues showed that human NPCs and placental cells are targeted by ZIKV. Also of concern is the impact of ZIKV on human reproductive structures, with the potential …
The Heat Shock Response And Humoral Immune Response Are Mutually Antagonistic In Honey Bees, Mia Mckinstry, Charlie Chung, Henry Truong, Brittany A. Johnston, Jonathan W. Snow
The Heat Shock Response And Humoral Immune Response Are Mutually Antagonistic In Honey Bees, Mia Mckinstry, Charlie Chung, Henry Truong, Brittany A. Johnston, Jonathan W. Snow
Publications and Research
The honey bee is of paramount importance to humans in both agricultural and ecological settings. Honey bee colonies have suffered from increased attrition in recent years, stemming from complex interacting stresses. Defining common cellular stress responses elicited by these stressors represents a key step in understanding potential synergies. The proteostasis network is a highly conserved network of cellular stress responses involved in maintaining the homeostasis of protein production and function. Here, we have characterized the Heat Shock Response (HSR), one branch of this network, and found that its core components are conserved. In addition, exposing bees to elevated temperatures normally …
Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi
Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi
Publications and Research
Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant …
Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy
Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy
Publications and Research
The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This …
The Replication Initiator Of The Cholera Pathogen’S Second Chromosome Shows Structural Similarity To Plasmid Initiators, Natalia Orlova, Matthew Gerding, Olha Ivashkiv, Paul Dominic B. Olinares, Brian T. Chait, Matthew K. Waldor, David Jeruzalmi
The Replication Initiator Of The Cholera Pathogen’S Second Chromosome Shows Structural Similarity To Plasmid Initiators, Natalia Orlova, Matthew Gerding, Olha Ivashkiv, Paul Dominic B. Olinares, Brian T. Chait, Matthew K. Waldor, David Jeruzalmi
Publications and Research
The conserved DnaA-oriC system is used to initiate replication of primary chromosomes throughout the bacterial kingdom; however, bacteria with multipartite genomes evolved distinct systems to initiate replication of secondary chromosomes. In the cholera pathogen, Vibrio cholerae, and in related species, secondary chromosome replication requires the RctB initiator protein. Here, we show that RctB consists of four domains. The structure of its central two domains resembles that of several plasmid replication initiators. RctB contains at least three DNA binding winged-helix-turn-helix motifs, and mutations within any of these severely compromise biological activity. In the structure, RctB adopts a headto- head dimeric configuration …
Characterization Of Fluorescent Proteins For Three- And Four-Color Live-Cell Imaging In S. Cerevisiae, Ryo Higuchi-Sanabria, Enrique J. Garcia, Delia Tomoiaga, Emilia L. Munteanu, Paul Feinstein, Liza A. Pon
Characterization Of Fluorescent Proteins For Three- And Four-Color Live-Cell Imaging In S. Cerevisiae, Ryo Higuchi-Sanabria, Enrique J. Garcia, Delia Tomoiaga, Emilia L. Munteanu, Paul Feinstein, Liza A. Pon
Publications and Research
Saccharomyces cerevisiae are widely used for imaging fluorescently tagged protein fusions. Fluorescent proteins can easily be inserted into yeast genes at their chromosomal locus, by homologous recombination, for expression of tagged proteins at endogenous levels. This is especially useful for incorporation of multiple fluorescent protein fusions into a single strain, which can be challenging in organisms where genetic manipulation is more complex. However, the availability of optimal fluorescent protein combinations for 3-color imaging is limited. Here, we have characterized a combination of fluorescent proteins, mTFP1/mCitrine/ mCherry for multicolor live cell imaging in S. cerevisiae. This combination can be used with …
Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman
Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman
Publications and Research
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …
Interferon-Γ Regulates Cellular Metabolism And Mrna Translation To Potentiate Macrophage Activation, Xiaodi Su, Yingpu Yu, Yi Zhong, Eugenia Giannopoulou, Xiaoyu Hu, Hui Liu, Justin R. Cross, Gunnar Rätsch, Charles M. Rice, Lionel B. Ivashkiv
Interferon-Γ Regulates Cellular Metabolism And Mrna Translation To Potentiate Macrophage Activation, Xiaodi Su, Yingpu Yu, Yi Zhong, Eugenia Giannopoulou, Xiaoyu Hu, Hui Liu, Justin R. Cross, Gunnar Rätsch, Charles M. Rice, Lionel B. Ivashkiv
Publications and Research
Interferon-γ (IFN-γ) primes macrophages for enhanced inflammatory activation by Toll-like receptors (TLRs) and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-γ regulates human macrophage metabolism and translation by targeting the kinases mTORC1 and MNK that both converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of mTORC1 by IFN-γ was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-γ selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and …
Autophagy Plays An Essential Role In Mediating Regression Of Hypertrophy During Unloading Of The Heart, Nirmala Hariharan, Yoshiyuki Ikeda, Chull Hong, Ralph R. Alcendor, Soichiro Usui, Shumin Gao, Yasuhiro Maejima, Junichi Sadoshima
Autophagy Plays An Essential Role In Mediating Regression Of Hypertrophy During Unloading Of The Heart, Nirmala Hariharan, Yoshiyuki Ikeda, Chull Hong, Ralph R. Alcendor, Soichiro Usui, Shumin Gao, Yasuhiro Maejima, Junichi Sadoshima
Publications and Research
Autophagy is a bulk degradation mechanism for cytosolic proteins and organelles. The heart undergoes hypertrophy in response to mechanical load but hypertrophy can regress upon unloading. We hypothesize that autophagy plays an important role in mediating regression of cardiac hypertrophy during unloading. Mice were subjected to transverse aortic constriction (TAC) for 1 week, after which the constriction was removed (DeTAC). Regression of cardiac hypertrophy was observed after DeTAC, as indicated by reduction of LVW/BW and cardiomyocyte cross-sectional area. Indicators of autophagy, including LC3-II expression, p62 degradation and GFP-LC3 dots/cell, were significantly increased after DeTAC, suggesting that autophagy is induced. Stimulation …
Dna Adducts Of Decarbamoyl Mitomycin C Efficiently Kill Cells Without Wild-Type P53 Resulting From Proteasome-Mediated Degradation Of Checkpoint Protein 1, Ernest K. Boamah, Angelika Brekman, Maria Tomasz, Natura Myeka, Maria E. Figueiredo-Pereira, Senyene Hunter, Joel Meyer, Rahul C. Bhosle, Jill Bargonetti
Dna Adducts Of Decarbamoyl Mitomycin C Efficiently Kill Cells Without Wild-Type P53 Resulting From Proteasome-Mediated Degradation Of Checkpoint Protein 1, Ernest K. Boamah, Angelika Brekman, Maria Tomasz, Natura Myeka, Maria E. Figueiredo-Pereira, Senyene Hunter, Joel Meyer, Rahul C. Bhosle, Jill Bargonetti
Publications and Research
The mitomycin derivative 10-decarbamoyl mitomycin C (DMC) more rapidly activates a p53-independent cell death pathway than mitomycin C (MC). We recently documented that an increased proportion of mitosene1-β-adduct formation occurs in human cells treated with DMC in comparison to those treated with MC. Here, we compare the cellular and molecular response of human cancer cells treated with MC and DMC. We find the increase in mitosene 1-β-adduct formation correlates with a condensed nuclear morphology and increased cytotoxicity in human cancer cells with or without p53. DMC caused more DNA damage than MC in the nuclear and mitochondrial genomes. Checkpoint 1 …