CUE Domain-Containing Protein Vps901 Is Required for Vacuolar Protein Transport in<i>Schizosaccharomyces pombe</i>

Nakase, Mai; Tsukamoto, Yuta; Hosomi, Akíra; Matsuda, Tomo; Miyamoto, Masaaki; Takegawa, Kaoru

doi:10.1271/bbb.110609

Cited by 3 publications

(3 citation statements)

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“…; Nakase et al . ) and chromosome segregation (Duo1, Dad2, Dad5, Spc19; microtubule–kinetochore connecting DASH complex subunits) (Liu et al . ).…”

Section: Resultsmentioning

confidence: 99%

“…In particular, genes encoding biosynthetic enzymes of the mitochondrial coenzyme Q pathway were not identified as DCR genes, suggesting that the disruption of coenzyme Q synthesis and/or disruption of mitochondrial membrane integrity may not contribute to calcium sensitivity. In addition, only a subset of transport regulators-Vps901, Vps35, Vph2 and Rav1-were identified as DCR genes, indicating that generalized membrane transport defects may not be associated with the cytotoxic effect of calcium (Iwaki et al 2006;Nakase et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The connection between SAGA and ER stress is probably reflected by the connection between the SAGA subunit Ngg1 and Rav1, which were co-isolated as hits in multiple sensitivity screens in fission yeast (Guo et al 2012;Tay et al 2013). An additional two smaller clusters were obtained for the DCR genes related to vacuolar transport (Vps35 and Vps901) (Iwaki et al 2006;Nakase et al 2012) and chromosome segregation (Duo1, Dad2, Dad5, Spc19; microtubule-kinetochore connecting DASH complex subunits) (Liu et al 2005).…”

Section: Determination Of a Functional Doxorubicin-and Calcium-resistmentioning

confidence: 99%

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Calcium modulation of doxorubicin cytotoxicity in yeast and human cells

et al. 2016

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Doxorubicin is a widely used chemotherapeutic agent, but its utility is limited by cellular resistance and off‐target effects. To understand the molecular mechanisms regulating chemotherapeutic responses to doxorubicin, we previously carried out a genomewide search of doxorubicin‐resistance genes in Schizosaccharomyces pombe fission yeast and showed that these genes are organized into networks that counteract doxorubicin cytotoxicity. Here, we describe the identification of a subgroup of doxorubicin‐resistance genes that, when disrupted, leads to reduced tolerance to exogenous calcium. Unexpectedly, we observed a suppressive effect of calcium on doxorubicin cytotoxicity, where concurrent calcium and doxorubicin treatment resulted in significantly higher cell survival compared with cells treated with doxorubicin alone. Conversely, inhibitors of voltage‐gated calcium channels enhanced doxorubicin cytotoxicity in the mutants. Consistent with these observations in fission yeast, calcium also suppressed doxorubicin cytotoxicity in human breast cancer cells. Further epistasis analyses in yeast showed that this suppression of doxorubicin toxicity by calcium was synergistically dependent on Rav1 and Vph2, two regulators of vacuolar‐ATPase assembly; this suggests potential modulation of the calcium–doxorubicin interaction by fluctuating proton concentrations within the cellular environment. Thus, the modulatory effects of drugs or diet on calcium concentrations should be considered in doxorubicin treatment regimes.

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“…; Nakase et al . ) and chromosome segregation (Duo1, Dad2, Dad5, Spc19; microtubule–kinetochore connecting DASH complex subunits) (Liu et al . ).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%