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The role of Connexin 46 promoter in lens and other hypoxic tissues.

Molina SA, Takemoto DJ - Commun Integr Biol (2012)

Bottom Line: The loss of Cx46 upregulates Cx43 in lens cell culture and suppresses tumor growth in breast and retinoblastoma tumor xenografts.Upregulation of Cx46 in hypoxic tissues has been noted and may be due in part to the effects of hypoxia and HIF activators.Here, we report that the Cx46 promoter is regulated by hypoxia and also offer speculation about the role of Cx46 in lens differentiation and solid tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry; Kansas State University; Manhattan, KS USA.

ABSTRACT
Gap junctions are multimeric membrane protein channels that connect the cytoplasm of one cell to another. Much information about connexins regards electrophysiology and channel function but relatively little information is known about non-channel functions of connexins. Lens connexins, Cx43, Cx46 and Cx50, have been extensively studied for their role in lens homeostasis. Connexins allow the movement of small metabolically relevant molecules and ions between cells and this action in the lens prevents cataract formation. Interruption of Cx46 channel function leads to cataract formation due to dysregulation of lens homeostasis. The loss of Cx46 upregulates Cx43 in lens cell culture and suppresses tumor growth in breast and retinoblastoma tumor xenografts. Upregulation of Cx46 in hypoxic tissues has been noted and may be due in part to the effects of hypoxia and HIF activators. Here, we report that the Cx46 promoter is regulated by hypoxia and also offer speculation about the role of Cx46 in lens differentiation and solid tumor growth.

No MeSH data available.


Related in: MedlinePlus

Figure 2. The promoter of human Connexin 46 is transiently responsive to 1% oxygen in human lens cells. Various fragments 5′ to the predicted transcription start site of the human Cx46 promoter were cloned into a promoterless luciferase reporter vector and tested for responsiveness to 1% oxygen in human lens epithelial cells. The varying activity correlated with the length of the promoter indicates the presence of regulatory elements encoded within the promoter. The promoter did not respond to hypoxia in N2A cells in the same assay (unpublished data). Error bars represent standard error of the mean (n = 6).
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Figure 2: Figure 2. The promoter of human Connexin 46 is transiently responsive to 1% oxygen in human lens cells. Various fragments 5′ to the predicted transcription start site of the human Cx46 promoter were cloned into a promoterless luciferase reporter vector and tested for responsiveness to 1% oxygen in human lens epithelial cells. The varying activity correlated with the length of the promoter indicates the presence of regulatory elements encoded within the promoter. The promoter did not respond to hypoxia in N2A cells in the same assay (unpublished data). Error bars represent standard error of the mean (n = 6).

Mentions: When the human promoter of Cx46 was challenged with 1% oxygen in human lens cells and normalized to a HIF1α-responsive control promoter, a transient ~17-fold increase in activity was observed with the 482 bp promoter (Fig. 2). HREs are most likely located within the proximal promoter region of less than 500 bp upstream of the TSS. The Cx46 promoter also showed sustained responses with shorter promoter fragments, suggesting that transcriptional regulation of Cx46 gene expression is tightly controlled by one or more positive and/or negative regulatory elements present beyond the proximal promoter region. The basal promoter still remains to be identified, but given the expression profile of the promoter fragments, it is likely located in the first 200 bp upstream of the TSS. Of course, the possibility of long-range transcriptional regulatory effects remains open.


The role of Connexin 46 promoter in lens and other hypoxic tissues.

Molina SA, Takemoto DJ - Commun Integr Biol (2012)

Figure 2. The promoter of human Connexin 46 is transiently responsive to 1% oxygen in human lens cells. Various fragments 5′ to the predicted transcription start site of the human Cx46 promoter were cloned into a promoterless luciferase reporter vector and tested for responsiveness to 1% oxygen in human lens epithelial cells. The varying activity correlated with the length of the promoter indicates the presence of regulatory elements encoded within the promoter. The promoter did not respond to hypoxia in N2A cells in the same assay (unpublished data). Error bars represent standard error of the mean (n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376042&req=5

Figure 2: Figure 2. The promoter of human Connexin 46 is transiently responsive to 1% oxygen in human lens cells. Various fragments 5′ to the predicted transcription start site of the human Cx46 promoter were cloned into a promoterless luciferase reporter vector and tested for responsiveness to 1% oxygen in human lens epithelial cells. The varying activity correlated with the length of the promoter indicates the presence of regulatory elements encoded within the promoter. The promoter did not respond to hypoxia in N2A cells in the same assay (unpublished data). Error bars represent standard error of the mean (n = 6).
Mentions: When the human promoter of Cx46 was challenged with 1% oxygen in human lens cells and normalized to a HIF1α-responsive control promoter, a transient ~17-fold increase in activity was observed with the 482 bp promoter (Fig. 2). HREs are most likely located within the proximal promoter region of less than 500 bp upstream of the TSS. The Cx46 promoter also showed sustained responses with shorter promoter fragments, suggesting that transcriptional regulation of Cx46 gene expression is tightly controlled by one or more positive and/or negative regulatory elements present beyond the proximal promoter region. The basal promoter still remains to be identified, but given the expression profile of the promoter fragments, it is likely located in the first 200 bp upstream of the TSS. Of course, the possibility of long-range transcriptional regulatory effects remains open.

Bottom Line: The loss of Cx46 upregulates Cx43 in lens cell culture and suppresses tumor growth in breast and retinoblastoma tumor xenografts.Upregulation of Cx46 in hypoxic tissues has been noted and may be due in part to the effects of hypoxia and HIF activators.Here, we report that the Cx46 promoter is regulated by hypoxia and also offer speculation about the role of Cx46 in lens differentiation and solid tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry; Kansas State University; Manhattan, KS USA.

ABSTRACT
Gap junctions are multimeric membrane protein channels that connect the cytoplasm of one cell to another. Much information about connexins regards electrophysiology and channel function but relatively little information is known about non-channel functions of connexins. Lens connexins, Cx43, Cx46 and Cx50, have been extensively studied for their role in lens homeostasis. Connexins allow the movement of small metabolically relevant molecules and ions between cells and this action in the lens prevents cataract formation. Interruption of Cx46 channel function leads to cataract formation due to dysregulation of lens homeostasis. The loss of Cx46 upregulates Cx43 in lens cell culture and suppresses tumor growth in breast and retinoblastoma tumor xenografts. Upregulation of Cx46 in hypoxic tissues has been noted and may be due in part to the effects of hypoxia and HIF activators. Here, we report that the Cx46 promoter is regulated by hypoxia and also offer speculation about the role of Cx46 in lens differentiation and solid tumor growth.

No MeSH data available.


Related in: MedlinePlus