Michael Boyce

Overview:

The Boyce Lab studies mammalian cell signaling through protein glycosylation. For the latest news, project information and publications from our group, please visit our web site at http://www.boycelab.org or follow us on Twitter at https://twitter.com/BoyceLab.

Positions:

Associate Professor of Biochemistry

Biochemistry
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2005

Harvard Medical School

Grants:

Control of COPII vesicle trafficking by intracellular protein glycosylation

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein glycosylation in cancer cell signaling and metabolism

Administered By
Biochemistry
Role
Principal Investigator
Start Date
End Date

Control of COPII vesicle trafficking by intracellular protein glycosylation

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

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

Glycan biosynthesis relies on nucleotidesugars (NS), 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 dysregulated in disease, but how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, we examined uridine diphosphate (UDP)-galactose 4'-epimerase (GALE), which interconverts two pairs of essential NSs. GALE deletion in human cells triggered major imbalances in its substrate NSs and consequent dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the death receptor Fas. NS dysregulation also directly impacted cell signaling, as GALE-/- cells exhibit Fas hypoglycosylation and hypersensitivity to Fas ligand-induced apoptosis. Our results reveal a new role for GALE-mediated NS regulation in supporting death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.
Authors
Broussard, A; Florwick, A; Desbiens, C; Nischan, N; Robertson, C; Guan, Z; Kohler, JJ; Wells, L; Boyce, M
MLA Citation
Broussard, Alex, et al. “The human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function..” J Biol Chem, Dec. 2019. Pubmed, doi:10.1074/jbc.RA119.009271.
URI
https://scholars.duke.edu/individual/pub1423433
PMID
31819007
Source
pubmed
Published In
The Journal of Biological Chemistry
Published Date
DOI
10.1074/jbc.RA119.009271

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

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), in which IF proteins accumulate and aggregate in axons throughout the nervous system, impairing neuronal function and viability. Despite this pathophysiological significance, the upstream regulation and downstream effects of normal and aberrant gigaxonin function remain incompletely understood. Here, we report that gigaxonin is modified by O-linked-beta-N-acetylglucosamine (O-GlcNAc), a prevalent form of intracellular glycosylation, in a nutrient- and growth factor-dependent manner. Mass spectrometry analyses of human gigaxonin revealed nine candidate sites of O-GlcNAcylation, two of which - serine 272 and threonine 277 - are required for its ability to mediate IF turnover in novel gigaxonin-deficient human cell models that we created. Taken together, these results suggest that nutrient-responsive gigaxonin O-GlcNAcylation forms a regulatory link between metabolism and IF proteostasis. Our work may have significant implications for understanding the non-genetic modifiers of GAN phenotypes and for the optimization of gene therapy for this disease.
Authors
CHEN, PO-HAN; Smith, T; Hu, J; Pan, S; Smith, A; Lu, A; Chi, J-T; Boyce, M
URI
https://scholars.duke.edu/individual/pub1425510
Source
epmc
Published Date
DOI
10.1101/530303

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

© Copyright © 2019 Luo and Boyce. 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 genetic levels. However, we know much less about how cells dynamically modulate COPI trafficking in response to changing signals, metabolic state, stress or other stimuli. Recently, post-translational modifications (PTMs) have emerged as one common theme in the regulation of the COPI pathway. Here, we review a range of modifications and mechanisms that govern COPI activity in interphase cells and suggest potential future directions to address as-yet unanswered questions.
Authors
Luo, PM; Boyce, M
MLA Citation
Luo, P. M., and M. Boyce. “Directing Traffic: Regulation of COPI Transport by Post-translational Modifications.” Frontiers in Cell and Developmental Biology, vol. 7, Sept. 2019. Scopus, doi:10.3389/fcell.2019.00190.
URI
https://scholars.duke.edu/individual/pub1415390
Source
scopus
Published In
Frontiers in Cell and Developmental Biology
Volume
7
Published Date
DOI
10.3389/fcell.2019.00190

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

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 between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development.
Authors
Zentella, R; Hu, J; Hsieh, W-P; Matsumoto, PA; Dawdy, A; Barnhill, B; Oldenhof, H; Hartweck, LM; Maitra, S; Thomas, SG; Cockrell, S; Boyce, M; Shabanowitz, J; Hunt, DF; Olszewski, NE; Sun, T-P
MLA Citation
Zentella, Rodolfo, et al. “O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis..” Genes Dev, vol. 30, no. 2, Jan. 2016, pp. 164–76. Pubmed, doi:10.1101/gad.270587.115.
URI
https://scholars.duke.edu/individual/pub1119143
PMID
26773002
Source
pubmed
Published In
Genes Dev
Volume
30
Published Date
Start Page
164
End Page
176
DOI
10.1101/gad.270587.115

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

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 the activity. Based on the SAR results, salubrinal was converted into a biotinylated derivative which retains activity and can be used as a biological tool for target identification.
Authors
Long, K; Boyce, M; Lin, H; Yuan, J; Ma, D
MLA Citation
Long, Kai, et al. “Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative..” Bioorg Med Chem Lett, vol. 15, no. 17, Sept. 2005, pp. 3849–52. Pubmed, doi:10.1016/j.bmcl.2005.05.120.
URI
https://scholars.duke.edu/individual/pub808786
PMID
16002288
Source
pubmed
Published In
Bioorganic & Medicinal Chemistry Letters
Volume
15
Published Date
Start Page
3849
End Page
3852
DOI
10.1016/j.bmcl.2005.05.120