Sphingolipids signal heat stress-induced ubiquitin-dependent proteolysis.
Sphingolipids are essential eukaryotic membrane lipids that are structurally and metabolically conserved through evolution. Sphingolipids have also been proposed to regulate eukaryotic stress responses as novel second messengers. Here we show that, in Saccharomyces cerevisiae, phytosphingosine, a putative sphingolipid second messenger, mediates heat stress signaling and activates ubiquitin-dependent proteolysis via the endocytosis vacuolar degradation and 26 S proteasome pathways. Inactivation of serine palmitoyltransferase, a key enzyme in generating endogenous phytosphingosine, prevents proteolysis during heat stress. Addition of phytosphingosine bypasses the requirement for serine palmitoyltransferase and restores proteolysis. Phytosphingosine-induced proteolysis requires multiubiquitin chain formation through the stress-responsive lysine 63 residue of ubiquitin. We propose that heat stress increases phytosphingosine and activates ubiquitin-dependent proteolysis.
Chung
N
N
Program in Molecular Cancer Biology, Department of Pharmacology and Cancer Biology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Jenkins
G
G
Hannun
Y A
YA
Heitman
J
J
Obeid
L M
LM
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D006358:Hot Temperature; D008239:Lysine; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*; D051102:Serine C-Palmitoyltransferase; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D013172:Spores, Fungal; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism*; D014617:Vacuoles / Q000502:physiology
D014452:Ubiquitins; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C012491:phytosphingosine; D008239:Lysine; D013110:Sphingosine