Deregulation of the first N-glycosylation gene, ALG7, perturbs the expression of G1 cyclins and cell cycle arrest in Saccharomyces cerevisiae.
The evolutionarily conserved ALG7 gene encodes the dolichol-P-dependent N-acetylglucosamine-1-P transferase (GPT) and functions by initiating the dolichol pathway of protein N-glycosylation. In Saccharomyces cerevisiae, ALG7 has been shown to play a role in cell proliferation. The yeast alpha-factor-induced cell cycle arrest in G1 occurs, in part, by downregulation of CLN1 and CLN2. The function of ALG7 in G1 arrest was examined in alg7 mutants containing diminished GPT activity. In wild type, CLN1 and CLN2 mRNAs were rapidly downregulated, while in alg7 mutants, these transcripts were only transiently repressed before becoming greatly augmented. Analyses of DNA contents and budding indices showed that alg7 mutants resumed cycling when wild type cells remained arrested. Thus, deregulation of ALG7 interferes with cell cycle arrest by preventing a sustained downregulation of CLN1 and CLN2 mRNAs. These results provide a molecular insight into the role of ALG7, and protein N-glycosylation in general, in proliferation.
Lennon
K
K
Division of Oral Biology, Boston University School of Dental Medicine, Massachusetts, USA.
Bird
A
A
Kukuruzinska
M A
MA
D002453:Cell Cycle / Q000235:genetics*; D016213:Cyclins / Q000096:biosynthesis*; D005434:Flow Cytometry; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006031:Glycosylation; D006657:Histones / Q000096:biosynthesis; D000072235:Mating Factor; D010455:Peptides / Q000494:pharmacology; D010675:Pheromones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D017855:Transferases (Other Substituted Phosphate Groups) / Q000096:biosynthesis* / Q000235:genetics
D016213:Cyclins; D006657:Histones; D010455:Peptides; D010675:Pheromones; D012333:RNA, Messenger; D000072235:Mating Factor; D017855:Transferases (Other Substituted Phosphate Groups); C023222:UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase