Fission yeast Int6 is not essential for global translation initiation, but deletion of int6(+) causes hypersensitivity to caffeine and affects spore formation.
Mammalian INT6 protein has been considered to be a subunit of the eukaryotic translation initiation factor, eIF3. The Int6 locus is also known as a common integration site of mouse mammary tumor virus (MMTV). However, the function of Int6 in translation initiation and the mechanism of Int6-mediated tumor induction are yet to be explored. In this study, the fission yeast, Schizosaccharomyces pombe, int6(+), which is 43% identical to the mammalian counterpart, was deleted. Despite the evidence that the majority of Int6 protein was associated with 40S particles in this organism, strains lacking int6(+) (Deltaint6) were viable and showed only moderate inhibition in the rate of in vivo global protein synthesis. Polysome profile analysis showed no apparent defects in translation initiation. Deltaint6 exhibited a hypersensitivity to caffeine, which could be suppressed by the addition of sorbitol to the growth medium. This and other phenotypes would imply that int6(+) is required for the integrity of cell membrane. In meiosis, Deltaint6 produced incomplete tetrads frequently. High dosage expression of a truncated mutant of int6(+) conferred a hypersensitivity to caffeine, but did not cause the defect in meiosis. A possible link between the function of int6(+) and the Deltaint6-phenotypes is discussed.
Bandyopadhyay
A
A
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine of Yeshiva University, Jack and Pearl Resnick Campus, Bronx, New York 10461, USA.
Matsumoto
T
T
Maitra
U
U
D000595:Amino Acid Sequence; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002455:Cell Division / Q000235:genetics; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3; D017353:Gene Deletion; D008540:Meiosis; D051379:Mice; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000378:metabolism; D039665:Prokaryotic Initiation Factor-3; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012358:RNA, Transfer, Met / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013172:Spores, Fungal / Q000187:drug effects
D039621:Eukaryotic Initiation Factor-3; D010448:Peptide Initiation Factors; D039665:Prokaryotic Initiation Factor-3; D011518:Proto-Oncogene Proteins; D012358:RNA, Transfer, Met; D002110:Caffeine