RRC ID 12696
Author Morita T, Satoh R, Umeda N, Kita A, Sugiura R.
Title The stress granule protein Vgl1 and poly(A)-binding protein Pab1 are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe.
Journal Biochem Biophys Res Commun
Abstract Doxorubicin is an anthracycline antibiotic widely used for chemotherapy. Although doxorubicin is effective in the treatment of several cancers, including solid tumors and leukemias, the basis of its mechanism of action is not completely understood. Here, we describe the effects of doxorubicin and its relationship with stress granules formation in the fission yeast, Schizosaccharomyces pombe. We show that disruption of genes encoding the components of stress granules, including vgl1(+), which encodes a multi-KH type RNA-binding protein, and pab1(+), which encodes a poly(A)-binding protein, resulted in greater sensitivity to doxorubicin than seen in wild-type cells. Disruption of the vgl1(+) and pab1(+) genes did not confer sensitivity to other anti-cancer drugs such as cisplatin, 5-fluorouracil, and paclitaxel. We also showed that doxorubicin treatment promoted stress granule formation when combined with heat shock. Notably, doxorubicin treatment did not induce hyperphosphorylation of eIF2α, suggesting that doxorubicin is involved in stress granule assembly independent of eIF2α phosphorylation. Our results demonstrate the usefulness of fission yeast for elucidating the molecular targets of doxorubicin toxicity and suggest a novel drug-resistance mechanism involving stress granule assembly.
Volume 417(1)
Pages 399-403
Published 2012-1-6
DOI 10.1016/j.bbrc.2011.11.127
PII S0006-291X(11)02155-3
PMID 22172946
MeSH Antibiotics, Antineoplastic / pharmacology* Cytoplasmic Granules / metabolism Doxorubicin / pharmacology* Drug Resistance, Neoplasm* Poly(A)-Binding Protein I / genetics Poly(A)-Binding Protein I / metabolism* Poly(A)-Binding Proteins / genetics Poly(A)-Binding Proteins / metabolism* Schizosaccharomyces / drug effects* Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism*
IF 2.985
Times Cited 6
Yeast HM123