Journal ArticleNat Commun · October 17, 2023
The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly ...
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Journal ArticleIsr J Chem · February 2023
O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification in mammals, decorating thousands of intracellular proteins. O-GlcNAc cycling is an essential regulator of myriad aspects of cell physiology and is dysregulated in num ...
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Journal ArticleProc Natl Acad Sci U S A · August 2, 2022
Protein secretion is an essential process that drives cell growth, movement, and communication. Protein traffic within the secretory pathway occurs via transport intermediates that bud from one compartment and fuse with a downstream compartment to deliver ...
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Journal ArticleGlycobiology · September 20, 2021
O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic form of intracellular glycosylation common in animals, plants and other organisms. O-GlcNAcylation is essential in mammalian cells and is dysregulated in myriad human diseases, such as cancer, neurodeg ...
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Journal ArticleBMC Proc · June 22, 2021
At research-intensive universities in the United States, eligible faculty must generally excel in research, teaching and service in order to receive tenure. To meet these high standards, junior faculty should begin planning for a strong tenure case from th ...
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Journal ArticleCell Chem Biol · September 17, 2020
Glycan recognition is typically studied using free glycans, but glycopeptide presentations represent more physiological conditions for glycoproteins. To facilitate studies of glycopeptide recognition, we developed Glyco-SPOT synthesis, which enables the pa ...
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Journal ArticleSci Rep · May 18, 2020
The central goals of mechanobiology are to understand how cells generate force and how they respond to environmental mechanical stimuli. A full picture of these processes requires high-resolution, volumetric imaging with time-correlated force measurements. ...
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ConferenceThe FASEB Journal · April 2020
The Kelch‐like (KLHL) family of proteins, a conserved group of 42 human members, binds to E3 ubiquitin ligase complexes to target protein substrates for proteasomal degradation. Although mutations in KLHL genes cause various ...
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Journal ArticleJ Biol Chem · January 31, 2020
Glycan biosynthesis relies on nucleotide sugars (NSs), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulat ...
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Journal ArticleJCI Insight · January 16, 2020
Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), ...
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Journal ArticleJ Microbiol Biol Educ · 2020
Promoting diversity and inclusiveness in the STEM academic workforce remains a key challenge and national priority. Scientific societies can play a significant role in this process through the creation and implementation of programs to foster STEM academic ...
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Journal ArticleFront Cell Dev Biol · 2020
The coat protein complex II (COPII) mediates forward trafficking of protein and lipid cargoes from the endoplasmic reticulum. COPII is an ancient and essential pathway in all eukaryotes and COPII dysfunction underlies a range of human diseases. Despite thi ...
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Journal ArticleMol Biol Cell · March 1, 2019
Cells are dazzling in their diversity, both within and across organisms. And yet, throughout this variety runs at least one common thread: sugars. All cells on Earth, in all domains of life, are literally covered in glycans, a term referring to the carbohy ...
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Journal ArticleFront Cell Dev Biol · 2019
The coat protein complex I (COPI) is an essential, highly conserved pathway that traffics proteins and lipids between the endoplasmic reticulum (ER) and the Golgi. Many aspects of the COPI machinery are well understood at the structural, biochemical and ge ...
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Journal Article · 2019
Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), ...
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Journal ArticleGlycobiology · August 1, 2018
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and o ...
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Journal ArticleNat Commun · October 17, 2023
The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly ...
Full textLink to itemCite
Journal ArticleIsr J Chem · February 2023
O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification in mammals, decorating thousands of intracellular proteins. O-GlcNAc cycling is an essential regulator of myriad aspects of cell physiology and is dysregulated in num ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · August 2, 2022
Protein secretion is an essential process that drives cell growth, movement, and communication. Protein traffic within the secretory pathway occurs via transport intermediates that bud from one compartment and fuse with a downstream compartment to deliver ...
Full textLink to itemCite
Journal ArticleGlycobiology · September 20, 2021
O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic form of intracellular glycosylation common in animals, plants and other organisms. O-GlcNAcylation is essential in mammalian cells and is dysregulated in myriad human diseases, such as cancer, neurodeg ...
Full textLink to itemCite
Journal ArticleBMC Proc · June 22, 2021
At research-intensive universities in the United States, eligible faculty must generally excel in research, teaching and service in order to receive tenure. To meet these high standards, junior faculty should begin planning for a strong tenure case from th ...
Full textLink to itemCite
Journal ArticleCell Chem Biol · September 17, 2020
Glycan recognition is typically studied using free glycans, but glycopeptide presentations represent more physiological conditions for glycoproteins. To facilitate studies of glycopeptide recognition, we developed Glyco-SPOT synthesis, which enables the pa ...
Full textLink to itemCite
Journal ArticleSci Rep · May 18, 2020
The central goals of mechanobiology are to understand how cells generate force and how they respond to environmental mechanical stimuli. A full picture of these processes requires high-resolution, volumetric imaging with time-correlated force measurements. ...
Full textLink to itemCite
ConferenceThe FASEB Journal · April 2020
The Kelch‐like (KLHL) family of proteins, a conserved group of 42 human members, binds to E3 ubiquitin ligase complexes to target protein substrates for proteasomal degradation. Although mutations in KLHL genes cause various ...
Full textCite
Journal ArticleJ Biol Chem · January 31, 2020
Glycan biosynthesis relies on nucleotide sugars (NSs), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulat ...
Full textOpen AccessLink to itemCite
Journal ArticleJCI Insight · January 16, 2020
Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), ...
Full textLink to itemCite
Journal ArticleJ Microbiol Biol Educ · 2020
Promoting diversity and inclusiveness in the STEM academic workforce remains a key challenge and national priority. Scientific societies can play a significant role in this process through the creation and implementation of programs to foster STEM academic ...
Full textLink to itemCite
Journal ArticleFront Cell Dev Biol · 2020
The coat protein complex II (COPII) mediates forward trafficking of protein and lipid cargoes from the endoplasmic reticulum. COPII is an ancient and essential pathway in all eukaryotes and COPII dysfunction underlies a range of human diseases. Despite thi ...
Full textLink to itemCite
Journal ArticleMol Biol Cell · March 1, 2019
Cells are dazzling in their diversity, both within and across organisms. And yet, throughout this variety runs at least one common thread: sugars. All cells on Earth, in all domains of life, are literally covered in glycans, a term referring to the carbohy ...
Full textOpen AccessLink to itemCite
Journal ArticleFront Cell Dev Biol · 2019
The coat protein complex I (COPI) is an essential, highly conserved pathway that traffics proteins and lipids between the endoplasmic reticulum (ER) and the Golgi. Many aspects of the COPI machinery are well understood at the structural, biochemical and ge ...
Full textOpen AccessLink to itemCite
Journal Article · 2019
Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), ...
Full textOpen AccessCite
Journal ArticleGlycobiology · August 1, 2018
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and o ...
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Journal ArticleProc Natl Acad Sci U S A · June 5, 2018
O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events rema ...
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Journal ArticleElife · March 7, 2018
Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction. Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyop ...
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Journal ArticleBiochemistry · January 9, 2018
The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing ...
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Journal ArticleBiochemistry · January 9, 2018
O-Linked β-N-acetylglucosamine (O-GlcNAc) is a critical post-translational modification (PTM) of thousands of intracellular proteins. Reversible O-GlcNAcylation governs many aspects of cell physiology and is dysregulated in numerous human diseases. Despite ...
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Journal ArticleFront Endocrinol (Lausanne) · 2018
O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants. In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurod ...
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Journal ArticleChembiochem · September 19, 2017
Trehalose is a disaccharide produced by many organisms to better enable them to survive environmental stresses, including heat, cold, desiccation, and reactive oxygen species. Mammalian cells do not naturally biosynthesize trehalose; however, when introduc ...
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Journal ArticleEMBO J · August 1, 2017
O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations i ...
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Journal ArticleNat Chem Biol · May 2017
Plant development requires coordination among complex signaling networks to enhance the plant's adaptation to changing environments. DELLAs, transcription regulators originally identified as repressors of phytohormone gibberellin signaling, play a central ...
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Chapter · March 27, 2017
This book provides a thorough review of the current state of glycoprotein chemical biology, describing the development and application of glycoprotein and glycan synthesis technologies for understanding and manipulating protein ... ...
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Journal ArticleMol Cell Oncol · 2017
The KEAP1/NRF2 pathway is a master regulator of the redox stress response and is dysregulated in numerous human tumors. We discovered that NRF2 signaling is controlled by the site-specific glycosylation of KEAP1, revealing a potentially broad link among nu ...
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Journal ArticleGenes Dev · January 15, 2016
The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk ...
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Journal ArticleProc Natl Acad Sci U S A · March 27, 2012
O-linked β-N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modific ...
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Journal ArticleBioorg Med Chem Lett · September 1, 2011
Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycop ...
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Journal ArticleNat Methods · July 28, 2011
Bioorthogonal chemistry allows a wide variety of biomolecules to be specifically labeled and probed in living cells and whole organisms. Here we discuss the history of bioorthogonal reactions and some of the most interesting and important advances in the f ...
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Journal ArticleProc Natl Acad Sci U S A · February 22, 2011
Hundreds of mammalian nuclear and cytoplasmic proteins are reversibly glycosylated by O-linked β-N-acetylglucosamine (O-GlcNAc) to regulate their function, localization, and stability. Despite its broad functional significance, the dynamic and posttranslat ...
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Journal ArticleChembiochem · January 24, 2011
Several protein lysine methyltransferases (PKMTs) modify histones to regulate chromatin-dependent cellular processes, such as transcription, DNA replication and DNA damage repair. PKMTs are likely to have many additional substrates in addition to histones, ...
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Journal Article · January 1, 2011
Introduction The endoplasmic reticulum (ER) serves as the primary cellular protein processing factory where polypeptides destined for secretion or membrane insertion are folded. This membrane-bound organelle recruits translating ribosomes, translocates new ...
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Journal ArticleAutophagy · April 2009
The phosphorylation of the subunit alpha of eukaryotic translation initiation factor 2 (eIF2alpha), a critical regulatory event in controlling protein translation, has recently been found to mediate the induction of autophagy. However, the mediators of aut ...
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Journal ArticleVirology · September 30, 2008
The small molecule salubrinal has antiviral activity against herpes simplex virus-1 (HSV-1) and inhibits dephosphorylation of eIF2 alpha mediated by the HSV-1 protein ICP34.5. We investigated whether salubrinal's activities in infected cells depend on ICP3 ...
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Journal ArticleCell Death Differ · March 2008
Apoptosis triggered by endoplasmic reticulum (ER) stress has been implicated in many diseases but its cellular regulation remains poorly understood. Previously, we identified salubrinal (sal), a small molecule that protects cells from ER stress-induced apo ...
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Journal ArticleJ Cell Biol · November 19, 2007
Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic regulation relies on specialized cell death signaling pathways and also inte ...
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Journal ArticleJ Biol Chem · February 9, 2007
Free fatty acids cause pancreatic beta-cell apoptosis and may contribute to beta-cell loss in type 2 diabetes via the induction of endoplasmic reticulum stress. Reductions in eukaryotic translation initiation factor (eIF) 2alpha phosphorylation trigger bet ...
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Journal ArticleCell Death Differ · March 2006
The proper functioning of the endoplasmic reticulum (ER) is critical for numerous aspects of cell physiology. Accordingly, all eukaryotes react rapidly to ER dysfunction through a set of adaptive pathways known collectively as the ER stress response (ESR). ...
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Journal ArticleJ Mol Recognit · 2006
The three-dimensional structure of the 3' terminus of alfalfa mosaic virus RNA in complex with an amino-terminal coat protein peptide revealed an unusual RNA fold with inter-AUGC basepairing stabilized by key arginine residues (Guogas, et al., 2004). To pr ...
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Journal ArticleBioorg Med Chem Lett · September 1, 2005
The synthesis and structure-activity relationships (SAR) of salubrinal, a small molecule that protects cells from apoptosis induced by endoplasmic reticulum (ER) stress, are described. It is revealed that the trichloromethyl group greatly contributes to th ...
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Journal ArticleNat Chem Biol · July 2005
The mechanism of apoptosis has been extensively characterized over the past decade, but little is known about alternative forms of regulated cell death. Although stimulation of the Fas/TNFR receptor family triggers a canonical 'extrinsic' apoptosis pathway ...
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Journal ArticleScience · February 11, 2005
Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum ...
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Journal ArticleCell Death Differ · January 2004
Caspases are a family of cysteine proteases homologous to the Caenorhabditis elegans programmed cell death gene product CED-3. Caspases and their distant relatives, meta- and paracaspases, have been found in phylogenetically distant nonmetazoan groups, inc ...
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Journal ArticleOncogene · November 24, 2003
Caspases are a family of cysteine proteases that play important roles in regulating apoptosis. A decade of research has generated a wealth of information on the signal transduction pathways mediated by caspases, the distinct functions of individual caspase ...
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Journal ArticleNat Cell Biol · June 2002
Over 500 researchers participated in a recent American Association for Cancer Research special conference, entitled "Apoptosis and Cancer: Basic Mechanisms and Therapeutic Opportunities in the Post-Genomic Era" (February 13-17, 2002) in sunny Hawaii (Hilto ...
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Journal ArticleJ Cell Biol · November 26, 2001
The proapoptotic members of the Bcl-2 family have been proposed to participate in the formation of a channel that releases these apoptogenic factors when mitochondria receive apoptotic signals. A recent study provides the first direct, biophysical measurem ...
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