Scholars@Duke
Michael Scott Boyce

Michael Scott Boyce

Associate Professor of Biochemistry
Biochemistry
michael.boyce@duke.edu
Box 3711, Durham, NC 27710
208A Nanaline H Duke, Durham, NC 27710

Selected Publications

O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations.

Journal Article Nat 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 text Link to item Cite

The 2022 Nobel Prize in Chemistry-sweet!

Journal Article Glycobiology · April 19, 2023 Full text Link to item Cite

Chemical Biology Approaches to Understanding Neuronal O-GlcNAcylation.

Journal Article Isr 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 text Link to item Cite

Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export.

Journal Article Proc 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 text Link to item Cite

Evidence for nutrient-dependent regulation of the COPII coat by O-GlcNAcylation.

Journal Article Glycobiology · 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 text Link to item Cite

Preparing for tenure at a research-intensive university.

Journal Article BMC 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 text Link to item Cite

Parallel Glyco-SPOT Synthesis of Glycopeptide Libraries.

Journal Article Cell 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 text Link to item Cite

Combined Atomic Force Microscope and Volumetric Light Sheet System for Correlative Force and Fluorescence Mechanobiology Studies.

Journal Article Sci 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 text Link to item Cite

Kelch‐like Proteins Have A Sweet Spot: Site‐specific Glycosylation Influences Metabolic Regulation and Protein Homeostasis

Conference The 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 text Cite

Human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function.

Journal Article J 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 text Open Access Link to item Cite

Gigaxonin glycosylation regulates intermediate filament turnover and may impact giant axonal neuropathy etiology or treatment.

Journal Article JCI 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 text Link to item Cite

Scientific Societies Advancing STEM Workforce Diversity: Lessons and Outcomes from the Minorities Affairs Committee of the American Society for Cell Biology.

Journal Article J 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 text Link to item Cite

Export Control: Post-transcriptional Regulation of the COPII Trafficking Pathway.

Journal Article Front 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 text Link to item Cite

Life is sweet: the cell biology of glycoconjugates.

Journal Article Mol 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 text Open Access Link to item Cite

Directing Traffic: Regulation of COPI Transport by Post-translational Modifications.

Journal Article Front 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 text Open Access Link to item Cite

Glycosylation of gigaxonin regulates intermediate filaments: Novel molecular insights into giant axonal neuropathy

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 text Open Access Cite

Functional crosstalk among oxidative stress and O-GlcNAc signaling pathways.

Journal Article Glycobiology · 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 ... Full text Open Access Link to item Cite

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.

Journal Article Proc 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 ... Full text Open Access Link to item Cite

Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.

Journal Article Elife · 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 ... Full text Open Access Link to item Cite

Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway.

Journal Article Biochemistry · 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 ... Full text Open Access Link to item Cite

A Sweet Embrace: Control of Protein-Protein Interactions by O-Linked β-N-Acetylglucosamine.

Journal Article Biochemistry · 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 ... Full text Open Access Link to item Cite

A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.

Journal Article Front 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 ... Full text Open Access Link to item Cite

Esterified Trehalose Analogues Protect Mammalian Cells from Heat Shock.

Journal Article Chembiochem · 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 ... Full text Open Access Link to item Cite

Glycosylation of KEAP1 links nutrient sensing to redox stress signaling.

Journal Article EMBO 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 ... Full text Open Access Link to item Cite

The Arabidopsis O-fucosyltransferase SPINDLY activates nuclear growth repressor DELLA.

Journal Article Nat 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 ... Full text Open Access Link to item Cite

Chemical biology of O-GlcNAc glycosylation

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 ... ... Cite

KEAP1 has a sweet spot: A new connection between intracellular glycosylation and redox stress signaling in cancer cells.

Journal Article Mol 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 ... Full text Open Access Link to item Cite

O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis.

Journal Article Genes 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 ... Full text Open Access Link to item Cite

Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners.

Journal Article Proc 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 ... Full text Open Access Link to item Cite

Cell surface glycoproteomic analysis of prostate cancer-derived PC-3 cells.

Journal Article Bioorg 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 ... Full text Open Access Link to item Cite

Bringing chemistry to life.

Journal Article Nat 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 ... Full text Open Access Link to item Cite

Metabolic cross-talk allows labeling of O-linked beta-N-acetylglucosamine-modified proteins via the N-acetylgalactosamine salvage pathway.

Journal Article Proc 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 ... Full text Open Access Link to item Cite

A chemical method for labeling lysine methyltransferase substrates.

Journal Article Chembiochem · 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, ... Full text Open Access Link to item Cite

Endoplasmic reticulum stress response in cell death and cell survival

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 ... Full text Cite

A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses.

Journal Article Autophagy · 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 ... Full text Link to item Cite

ICP34.5-dependent and -independent activities of salubrinal in herpes simplex virus-1 infected cells.

Journal Article Virology · 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 ... Full text Link to item Cite

A pharmacoproteomic approach implicates eukaryotic elongation factor 2 kinase in ER stress-induced cell death.

Journal Article Cell 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 ... Full text Link to item Cite

A genome-wide RNAi screen reveals multiple regulators of caspase activation.

Journal Article J 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 ... Full text Open Access Link to item Cite

Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis.

Journal Article J 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 ... Full text Link to item Cite

Cellular response to endoplasmic reticulum stress: a matter of life or death.

Journal Article Cell 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). ... Full text Link to item Cite

Base-pairing potential identified by in vitro selection predicts the kinked RNA backbone observed in the crystal structure of the alfalfa mosaic virus RNA-coat protein complex.

Journal Article J 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 ... Full text Link to item Cite

Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative.

Journal Article Bioorg 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 ... Full text Open Access Link to item Cite

Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.

Journal Article Nat 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 ... Full text Open Access Link to item Cite

A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.

Journal Article Science · 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 ... Full text Open Access Link to item Cite

Caspases: an ancient cellular sword of Damocles.

Journal Article Cell 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 ... Full text Open Access Link to item Cite

A decade of caspases.

Journal Article Oncogene · 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 ... Full text Open Access Link to item Cite

Life and death in paradise.

Journal Article Nat 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 ... Full text Open Access Link to item Cite

The channel of death.

Journal Article J 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 ... Full text Open Access Link to item Cite