Myristoylcoa:Protein N‐Myristoyltransferase

Rudnick, David A.; McWherter, Charles A.; Gokel, George W.; Gordon, Jeffrey I.

doi:10.1002/9780470123133.ch5

Cited by 15 publications

(10 citation statements)

References 189 publications

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“…N-myristoylation targets modified proteins for cellular membranes [57, 58], and also modulates protein-protein interactions [58]. One proteasome subunit, Rpt2, is N-myristoylated.…”

Section: 4 Regulation Of Proteasomes By Ptmsmentioning

confidence: 99%

Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond

Cui

Scruggs

Gilda

et al. 2014

Journal of Molecular and Cellular Cardiology

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The ubiquitin-proteasome system (UPS) is the major intracellular degradation system, and its proper function is critical to the health and function of cardiac cells. Alterations in cardiac proteasomes have been linked to several pathological phenotypes, including cardiomyopathies, ischemia-reperfusion injury, heart failure, and hypertrophy. Defects in proteasome-dependent cellular protein homeostasis can be causal for the initiation and progression of certain cardiovascular diseases. Emerging evidence suggests that the UPS can specifically target proteins that govern pathological signaling pathways for degradation, thus altering downstream effectors and disease outcomes. Alterations in UPS-substrate interactions in disease occur, in part, due to direct modifications of 19S, 11S or 20S proteasome subunits. Post-translational modifications (PTMs) are one facet of this proteasomal regulation, with over 400 known phosphorylation sites, over 500 ubiquitination sites and 83 internal lysine acetylation sites, as well as multiple sites for caspase cleavage, glycosylation (such as O-GlcNAc modification), methylation, nitrosylation, oxidation, and sumoylation. Changes in cardiac proteasome PTMs, which occur in ischemia and cardiomyopathies, are associated with changes in proteasome activity and proteasome assembly; however several features of this regulation remain to be explored. In this review, we focus on how some of the less common PTMs affect proteasome function and alter cellular protein homeostasis.

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“…N-myristoylation targets modified proteins for cellular membranes [57, 58], and also modulates protein-protein interactions [58]. One proteasome subunit, Rpt2, is N-myristoylated.…”

Section: 4 Regulation Of Proteasomes By Ptmsmentioning

confidence: 99%

Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond

Cui

Scruggs

Gilda

et al. 2014

Journal of Molecular and Cellular Cardiology

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“…Myristate from myristoyl-coenzyme A (CoA) is covalently attached to the secondary glycine of target proteins by NMT increasing in hydrophobicity (24). Myristoylated protein more readily associates with membranes or takes part in hydrophobic proteinprotein interactions (24,41). Many Arfs, including ScArf3p, are N myristoylated (2,35).…”

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confidence: 99%

Aspergillus nidulans ArfB Plays a Role in Endocytosis and Polarized Growth

et al. 2008

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Filamentous fungi undergo polarized growth throughout most of their life cycles. The Spitzenkörper is an apical organelle composed primarily of vesicles that is unique to filamentous fungi and is likely to act as a vesicle supply center for tip growth. Vesicle assembly and trafficking are therefore important for hyphal growth. ADP ribosylation factors (Arfs), a group of small GTPase proteins, play an important role in nucleating vesicle assembly. Little is known about the role of Arfs in filamentous hyphal growth. We found that Aspergillus nidulans is predicted to encode six Arf family proteins. Analysis of protein sequence alignments suggests that A. nidulans ArfB shares similarity with ARF6 of Homo sapiens and Arf3p of Saccharomyces cerevisiae. An arfB null allele (arfB disrupted by a transposon [arfB::Tn]) was characterized by extended isotropic growth of germinating conidia followed by cell lysis or multiple, random germ tube emergence, consistent with a failure to establish polarity. The mutant germ tubes and hyphae that do form initially meander abnormally off of the axis of polarity and frequently exhibit dichotomous branching at cell apices, consistent with a defect in polarity maintenance. FM4-64 staining of the arfB::Tn strain revealed that another phenotypic characteristic seen for arfB::Tn is a reduction and delay in endocytosis. ArfB is myristoylated at its N terminus. Green fluorescent protein-tagged ArfB (ArfB::GFP) localizes to the plasma membrane and endomembranes and mutation (ArfB G2A ::GFP) of the N-terminal myristoylation motif disperses the protein to the cytoplasm rather than to the membranes. These results demonstrate that ArfB functions in endocytosis to play important roles in polarity establishment during isotropic growth and polarity maintenance during hyphal extension.

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“…The Rpt2 protein from S. cerevisiae also has a myristoylation motif at its N‐terminus (Maurer‐Stroh et al ., 2002) and its myristoylation was biochemically confirmed (Kimura et al ., 2003). Protein myristoylation is involved in membrane positioning of the proteins and hydrophobic protein–protein interaction (Rudnick et al ., 1993). As in Schizosaccharomyces pombe the proteasome is localized primarily in the nucleus and to a lesser extent to the cytosol (Wilkinson et al ., 1998), N‐myristoylation is more likely involved in a hydrophobic protein–protein interaction between Rpt2p orthologue, a 19S subunit protein and the hydrophobic inner barrel of the 20S particle.…”

Section: Resultsmentioning

confidence: 99%

“…NMT transfers myristate from myristoyl‐CoA to the N‐terminus of target proteins. The covalent linkage of myristate provides increased hydrophobicity allowing the target proteins to localize to cell membranes (Rudnick et al ., 1993; Johnson et al ., 1994a) and to take part in hydrophobic protein–protein interactions (Rudnick et al ., 1993).…”

Section: Introductionmentioning

confidence: 99%

A novel interaction between N‐myristoylation and the 26S proteasome during cell morphogenesis

Lee

Shaw²

2007

Molecular Microbiology

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SummaryN-myristoylation is a protein lipidation event in which myristate is covalently linked to the N-terminal glycine of target proteins. In Aspergillus nidulans, the N-myristoylation deficient swoF1 mutant was previously shown to lose cell polarity during the early morphogenic event of germ tube emergence. To further investigate this defect, we mutagenized swoF1 and recovered six partial suppressors designated ssf (suppressor of swoF1). The secondary mutations enabled swoF1 to partially bypass its growth defect. We characterized a frame-shift mutation in ssfA1, which encodes an alpha subunit of the 20S core particle of the 26S proteasome. Fewer ubiquitinated proteins accumulated in the swoF1 mutant compared with wild-type. In contrast, the swoF1;ssfA1 mutant accumulated higher levels of ubiquitinated proteins than wild-type. The swoF1 mutant was bypassed in the presence of the proteasome inhibitor, MG132. These results demonstrate that the swoF1 phenotype was caused, at least in part, by an increased activity of 26S proteasome-dependent proteolysis and suppression occurred by attenuating the 26S proteasome activity. This is the first report linking N-myristoylation and ubiquitin-proteasomedependent proteolysis during morphogenesis.

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Myristoylcoa:Protein N‐Myristoyltransferase

Cited by 15 publications

References 189 publications

Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond

Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond

Aspergillus nidulans ArfB Plays a Role in Endocytosis and Polarized Growth

A novel interaction between N‐myristoylation and the 26S proteasome during cell morphogenesis

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