A novel interaction between N-myristoylation and the 26S proteasome during cell morphogenesis.
N-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-proteasome-dependent proteolysis during morphogenesis.
Lee
Soo Chan
SC
Program for the Biology of Filamentous Fungi, Department of Plant Pathology and Microbiology, Texas A&M University, 2132 TAMU, College Station, TX 77843, USA.
Shaw
Brian D
BD
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D001233:Aspergillus nidulans / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D016764:Cell Polarity; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016153:Genes, Suppressor; D005816:Genetic Complementation Test; D007976:Leupeptins / Q000494:pharmacology; D009154:Mutation; D019814:Myristic Acid / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D012098:Reproduction / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D005656:Fungal Proteins; D007976:Leupeptins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D019814:Myristic Acid; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde