Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of Int-6, a component of the human translation initiation factor eIF3. Disruption of the murine Int-6 gene by mouse mammary tumor virus (MMTV) has been implicated previously in tumorigenesis, although the underlying mechanism is not yet understood. Fission yeast Int6 was shown to interact with other presumptive components of eIF3 in vivo, and was present in size fractions consistent with its incorporation into a 43S translation preinitiation complex. Drug resistance induced by Int6 overexpression was dependent on the AP-1 transcription factor Pap1, and was associated with increased abundance of Pap1-responsive mRNAs, but not with Pap1 relocalization. Fission yeast cells lacking the int6 gene grew slowly. This growth retardation could be corrected by the expression of full length Int6 of fission yeast or human origin, or by a C-terminal fragment of the fission yeast protein that also conferred drug resistance, but not by truncated human Int-6 proteins corresponding to the predicted products of MMTV-disrupted murine alleles. Studies in fission yeast may therefore help to explain the ways in which Int-6 function can be perturbed during MMTV-induced mammary tumorigenesis.

Type

Journal article

Journal

Mol Biol Cell

Publication Date

11/2000

Volume

11

Pages

3993 - 4003

Keywords

Amino Acid Sequence, Base Sequence, Basic-Leucine Zipper Transcription Factors, Benzimidazoles, Carbamates, Cell Division, Cytoplasm, DNA-Binding Proteins, Drug Resistance, Microbial, Eukaryotic Initiation Factor-3, Fungal Proteins, Fungicides, Industrial, Gene Expression Regulation, Fungal, Humans, Mammary Tumor Virus, Mouse, Molecular Sequence Data, Peptide Initiation Factors, Prokaryotic Initiation Factor-3, Proto-Oncogene Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Up-Regulation