Biomaterial Database

Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. 1994

T G Turi, and P Webster, and J K Rose

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.

The fungal metabolite brefeldin A (BFA) causes the inhibition of protein secretion and the disruption of the structure and function of the Golgi complex in mammalian cells. Here we show that BFA has identical effects in the fission yeast Schizosaccharomyces pombe which normally contains a Golgi complex of stacked cisternae similar to the Golgi complexes in animal cells. After treatment with BFA, secretion was inhibited, Golgi complexes disappeared, and there was an accumulation of endoplasmic reticulum. These results indicate that the effects of BFA in fungi are very similar to those in mammalian cells and provide direct evidence for an effect of BFA on Golgi morphology in fungi. Five spontaneous BFA-resistant mutants were isolated. Genetic analysis showed that the mutations conferring BFA resistance were dominant and in two separate linkage groups. One of the BFA-resistant mutations was found to be allelic to crm1, a gene affecting chromatin structure. All BFA-resistant mutants overexpressed a 20-kDa protein, and the corresponding gene obr1 was isolated and sequenced. However, obr1 overexpression was not sufficient to confer BFA resistance. Plasmids capable of conferring BFA resistance to wild type cells were isolated from libraries constructed from the two BFA-resistant mutants. These plasmids contain six different genes capable of conferring resistance when present in high copy. One of these genes encoded the transcription factor pap1, a homolog of the mammalian AP1 protein. The overexpression of pap1 probably confers BFA resistance indirectly by inducing expression of one or more other proteins. The isolation of several genes conferring BFA resistance suggests several mechanisms are involved.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D010957	Plasmids	Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.	Episomes,Episome,Plasmid
D003517	Cyclopentanes	A group of alicyclic hydrocarbons with the general formula R-C5H9.	Cyclopentadiene,Cyclopentadienes,Cyclopentene,Cyclopentenes,Cyclopentane
D004352	Drug Resistance, Microbial	The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D005656	Fungal Proteins	Proteins found in any species of fungus.	Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D006056	Golgi Apparatus	A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)	Golgi Complex,Apparatus, Golgi,Complex, Golgi
D000073718	Pancreatitis-Associated Proteins	C-type lectins that restrict growth of bacteria in the intestinal epithelia and have bactericidal activity against gram-positive and gram-negative bacteria. They also regulate proliferation and differentiation of KERATINOCYTES following injury. Human pancreatitis-associated protein-1 (Reg3a) is overexpressed by pancreatic ACINAR CELLS in patients with CHRONIC PANCREATITIS. It is also highly expressed by pancreatic, bladder, and gastrointestinal cancer cells and may serve as a diagnostic biomarker.	Regenerating Islet-Derived Protein,Pancreatitis-Associated Protein,Pancreatitis-Associated Protein-1,Regenerating Islet-Derived Protein 3,Regenerating Islet-Derived Proteins,Islet-Derived Protein, Regenerating,Pancreatitis Associated Protein,Pancreatitis Associated Protein 1,Pancreatitis Associated Proteins,Protein, Pancreatitis-Associated,Protein, Regenerating Islet-Derived,Regenerating Islet Derived Protein,Regenerating Islet Derived Protein 3,Regenerating Islet Derived Proteins
D000097606	Exportin 1 Protein	A karyopherin that functions in nuclear export of proteins and several classes of RNAs.	Chromosome Region Maintenance 1 Protein,Exportin 1,CRM1 protein,XPO1 protein