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Transcriptomic response of yeast cells to ATX1 deletion under different copper levels.

Cankorur-Cetinkaya A, Eraslan S, Kirdar B - BMC Genomics (2016)

Bottom Line: ATX1 deletants were allowed to recover full respiratory capacity in the presence of excess copper in growth environment.The present finding revealed the dispensability of Atx1p for the transfer of copper ions to Ccc2p and highlighted its possible role in the cell cycle regulation.The results also showed the potential of Saccharomyces cerevisiae as a model organism in studying the capacity of ATOX1 as a therapeutic target for lung cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Faculty of Engineering, Bogazici University, 34342, Istanbul, Turkey. ayca.cankorur@boun.edu.tr.

ABSTRACT

Background: Iron and copper homeostatic pathways are tightly linked since copper is required as a cofactor for high affinity iron transport. Atx1p plays an important role in the intracellular copper transport as a copper chaperone transferring copper from the transporters to Ccc2p for its subsequent insertion into Fet3p, which is required for high affinity iron transport.

Results: In this study, genome-wide transcriptional landscape of ATX1 deletants grown in media either lacking copper or having excess copper was investigated. ATX1 deletants were allowed to recover full respiratory capacity in the presence of excess copper in growth environment. The present study revealed that iron ion homeostasis was not significantly affected by the absence of ATX1 either at the transcriptional or metabolic levels, suggesting other possible roles for Atx1p in addition to its function as a chaperone in copper-dependent iron absorption. The analysis of the transcriptomic response of atx1∆/atx1∆ and its integration with the genetic interaction network highlighted for the first time, the possible role of ATX1 in cell cycle regulation, likewise its mammalian counterpart ATOX1, which was reported to play an important role in the copper-stimulated proliferation of non-small lung cancer cells.

Conclusions: The present finding revealed the dispensability of Atx1p for the transfer of copper ions to Ccc2p and highlighted its possible role in the cell cycle regulation. The results also showed the potential of Saccharomyces cerevisiae as a model organism in studying the capacity of ATOX1 as a therapeutic target for lung cancer therapy.

No MeSH data available.


Related in: MedlinePlus

Clustering of the genes which show significant interaction effect. This figure contains the average normalized expression of the genes in each cluster that are significantly and differentially expressed in response to the interacting effect of gene deletion and copper level. Error bars indicate the confidence interval around the centroids. Blue and orange represents the average level of expression in the ATX1 deleted cells under copper deficient and high copper containing conditions, respectively. Grey and yellow represents the average level of expression in the reference strain under copper deficient and high copper containing conditions, respectively
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Fig2: Clustering of the genes which show significant interaction effect. This figure contains the average normalized expression of the genes in each cluster that are significantly and differentially expressed in response to the interacting effect of gene deletion and copper level. Error bars indicate the confidence interval around the centroids. Blue and orange represents the average level of expression in the ATX1 deleted cells under copper deficient and high copper containing conditions, respectively. Grey and yellow represents the average level of expression in the reference strain under copper deficient and high copper containing conditions, respectively

Mentions: To further classify these transcripts according to their level of expression under studied conditions, Self-Organizing Maps (SOM) [18] was used for clustering. These transcripts could be clustered into 6 different clusters based on their level of expression and the enriched GO biological processes among these clusters were identified (Fig. 2).Fig. 2


Transcriptomic response of yeast cells to ATX1 deletion under different copper levels.

Cankorur-Cetinkaya A, Eraslan S, Kirdar B - BMC Genomics (2016)

Clustering of the genes which show significant interaction effect. This figure contains the average normalized expression of the genes in each cluster that are significantly and differentially expressed in response to the interacting effect of gene deletion and copper level. Error bars indicate the confidence interval around the centroids. Blue and orange represents the average level of expression in the ATX1 deleted cells under copper deficient and high copper containing conditions, respectively. Grey and yellow represents the average level of expression in the reference strain under copper deficient and high copper containing conditions, respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940881&req=5

Fig2: Clustering of the genes which show significant interaction effect. This figure contains the average normalized expression of the genes in each cluster that are significantly and differentially expressed in response to the interacting effect of gene deletion and copper level. Error bars indicate the confidence interval around the centroids. Blue and orange represents the average level of expression in the ATX1 deleted cells under copper deficient and high copper containing conditions, respectively. Grey and yellow represents the average level of expression in the reference strain under copper deficient and high copper containing conditions, respectively
Mentions: To further classify these transcripts according to their level of expression under studied conditions, Self-Organizing Maps (SOM) [18] was used for clustering. These transcripts could be clustered into 6 different clusters based on their level of expression and the enriched GO biological processes among these clusters were identified (Fig. 2).Fig. 2

Bottom Line: ATX1 deletants were allowed to recover full respiratory capacity in the presence of excess copper in growth environment.The present finding revealed the dispensability of Atx1p for the transfer of copper ions to Ccc2p and highlighted its possible role in the cell cycle regulation.The results also showed the potential of Saccharomyces cerevisiae as a model organism in studying the capacity of ATOX1 as a therapeutic target for lung cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Faculty of Engineering, Bogazici University, 34342, Istanbul, Turkey. ayca.cankorur@boun.edu.tr.

ABSTRACT

Background: Iron and copper homeostatic pathways are tightly linked since copper is required as a cofactor for high affinity iron transport. Atx1p plays an important role in the intracellular copper transport as a copper chaperone transferring copper from the transporters to Ccc2p for its subsequent insertion into Fet3p, which is required for high affinity iron transport.

Results: In this study, genome-wide transcriptional landscape of ATX1 deletants grown in media either lacking copper or having excess copper was investigated. ATX1 deletants were allowed to recover full respiratory capacity in the presence of excess copper in growth environment. The present study revealed that iron ion homeostasis was not significantly affected by the absence of ATX1 either at the transcriptional or metabolic levels, suggesting other possible roles for Atx1p in addition to its function as a chaperone in copper-dependent iron absorption. The analysis of the transcriptomic response of atx1∆/atx1∆ and its integration with the genetic interaction network highlighted for the first time, the possible role of ATX1 in cell cycle regulation, likewise its mammalian counterpart ATOX1, which was reported to play an important role in the copper-stimulated proliferation of non-small lung cancer cells.

Conclusions: The present finding revealed the dispensability of Atx1p for the transfer of copper ions to Ccc2p and highlighted its possible role in the cell cycle regulation. The results also showed the potential of Saccharomyces cerevisiae as a model organism in studying the capacity of ATOX1 as a therapeutic target for lung cancer therapy.

No MeSH data available.


Related in: MedlinePlus