Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We have investigated the usefulness of the fission yeast Schizosaccharomyces pombe as a model organism for the discovery of novel modes of drug resistance in human cells. In fission yeast, overexpression of the essential pad1(+) gene confers pleiotropic drug resistance through a pathway involving an AP-1 transcription factor encoded by pap1(+). We have identified POH1, a human pad1 homologue that can substitute fully for pad1(+) and induce AP-1-dependent drug resistance in fission yeast. POH1 also confers P-glycoprotein-independent resistance to taxol (paclitaxel), doxorubicin, 7-hydroxystaurosporine, and ultraviolet light when transiently overexpressed in mammalian cells. Poh1 is a previously unidentified component of the human 26 S proteasome, a multiprotein complex that degrades proteins targeted for destruction by the ubiquitin pathway. Hence, Poh1 is part of a conserved mechanism that determines cellular susceptibility to cytotoxic agents, perhaps by influencing the ubiquitin-dependent proteolysis of transcription factors.


Journal article


J Biol Chem

Publication Date





30470 - 30475


Amino Acid Sequence, Animals, COS Cells, Cloning, Molecular, Cysteine Endopeptidases, Doxorubicin, Drug Resistance, Multiple, Genes, Fungal, Humans, Molecular Sequence Data, Multienzyme Complexes, Pancreatitis-Associated Proteins, Proteasome Endopeptidase Complex, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factor AP-1