Anti-cancer drug KP1019 induces Hog1 phosphorylation and protein ubiquitylation in Saccharomyces cerevisiae

Singh, Vikash; Azad, Gajendra Kumar; Reddy, Mahendranath; Baranwal, Shivani; Tomar, Raghuvir Singh

doi:10.1016/j.ejphar.2014.04.032

Cited by 22 publications

(23 citation statements)

References 37 publications

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“…More importantly, using HCCLM6 cells, endogenous Bcl-2 was shown to interact with endogenous Beclin-1 by co-immunoprecipitation (Fig. 35 To date, a plethora of rutheniumbased drugs have been synthesized. L-WH0402 (0.625 mM) treatment resulted in significantly less Bcl-2 co-precipitation with Beclin-1 compared with a vehicle group, although similar amounts of loading control were precipitated (Fig.…”

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confidence: 99%

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

et al. 2015

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To evaluate the anticancer mechanism of the new ruthenium complex-Λ-WH0402 at the cellular level, the in vitro cytotoxicity of Λ-WH0402 was investigated on 10 human tumor cell lines. Λ-WH0402 was found to have higher anticancer activity than cisplatin toward human liver cancer HCCLM6 cells that have high tumor metastatic characteristics. Meanwhile, Λ-WH0402 showed an antimetastatic effect on HCCLM6 cells in vitro, mostly through its effect on cell adhesion, invasion and migration. In addition, Λ-WH0402 significantly reduced tumor metastasis to the lungs in orthotopic mouse hepatocellular cancer (HCC) models induced by HCCLM6 cells. Furthermore, Λ-WH0402 exerted an inhibitory effect on tumor cell growth and proliferation and induced dose-dependent cell cycle arrest in the S phase in HCCLM6 cells. Immunoblotting analysis showed that Λ-WH0402 not only decreased the expression of antiapoptotic protein Bcl-2 and nutrient-deprivation autophagy factor-1 (NAF-1), but also significantly increased the expression of Beclin-1 in HCCLM6 cells. More importantly, we identified that Λ-WH0402 treatment reduced the interaction between Bcl-2 and Beclin-1, and increased the expression of autophagic activation marker LC3B-II in HCCLM6 cells. On the whole, our results suggested that the anitcancer activity of Λ-WH0402 is mediated through promoting the Beclin-1-dependent autophagy pathway in HCCLM6 cells.

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Section: View Article Onlinementioning

confidence: 99%

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

et al. 2015

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“…[27][28][29] Moreover, the drug bound readily with cytoplasmic proteins and mitochondria of fractionated yeast cells. 30 KP1019's ability to induce stress is also consistent with its ability to activate the evolutionarily conserved stress-responsive kinase Hog1 31 and to increase lipid droplet formation. 32 Combined, these studies suggest that KP1019 has multiple modes of action in yeast, much like it has in cultured mammalian cells.…”

Section: Introductionmentioning

confidence: 57%

“…101,102 Thus KP1019-dependent reductions in the levels of these proteins may contribute to the previously observed ability of the drug to result in global increases in ubiquitination. 31 Regardless of the mechanism(s) by which KP1019 impacts protein folding and turnover, bioinformatics (YeastMine) analysis implicated the evolutionarily conserved transcription factor Hsf1 as a potential contributor to KP1019-dependent changes in protein levels. A reporter assay supported this conclusion (Fig.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of the S. cerevisiae response to the anticancer ruthenium complex KP1019

et al. 2020

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“…Exponentially growing wild‐type and mutant yeast cells were harvested at OD 600 = 1.5. Total RNA was extracted by a heat/freeze phenol method as described earlier[42,43]. Approximately 1 μg of total RNA was reverse transcribed to synthesize cDNA using a High Capacity RNA‐to‐cDNA kit (Bio‐Rad) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Flocculation inSaccharomyces cerevisiae is regulated by RNA/DNA helicase Sen1p

Singh¹,

Azad²,

Sariki³

et al. 2015

FEBS Letters

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a b s t r a c tThe Nrd1-Nab3-Sen1 (NNS) complex terminates transcription of non-coding RNA genes and mediates degradation of the produced transcript by the nuclear exosome. The NNS complex also represses some stress response genes, by stimulating premature termination. A well-characterized stress response in yeast is flocculation, where cells aggregate to form flocs under expression of lectin-encoding genes designated as FLOs. In this study, we demonstrated the role of the NNS complex and Rrp6p in the expression of flocculation genes: FLO1, FLO5, FLO9, and FLO10. Furthermore, a deletion mutant of the RNA processing machinery (RNT1), and SEN1 mutants that are unable to interact with Rnt1p, exhibit a flocculation phenotype. In summary, we have identified a cooperative role of Rnt1p, Rrp6p and the NNS complex in the repression of FLO genes.

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Anti-cancer drug KP1019 induces Hog1 phosphorylation and protein ubiquitylation in Saccharomyces cerevisiae

Cited by 22 publications

References 37 publications

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

Proteomic analysis of the S. cerevisiae response to the anticancer ruthenium complex KP1019

Flocculation inSaccharomyces cerevisiae is regulated by RNA/DNA helicase Sen1p

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