PTH regulation of the human cytomegalovirus immediate-early gene promoter

Johann Herberth; Alexander P. Alimov; John P. Williams; Hartmut H. Malluche; Nicholas J. Koszewski

doi:10.1016/j.bbrc.2008.02.019

PTH regulation of the human cytomegalovirus immediate-early gene promoter

Johann Herberth
, Alexander P. Alimov
, John P. Williams
, Hartmut H. Malluche
, Nicholas J. Koszewski

Internal Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Secondary hyperparathyroidism and human cytomegalovirus (hCMV) seropositivity are highly prevalent in patients undergoing renal transplantation, and both are linked to the development of chronic allograft nephropathy (CAN). We investigated the hypothesis that parathyroid hormone (PTH) 1-84 regulates hCMV immediate-early gene (IEG) promoter activation in proximal renal tubular cells. PTH 1-84 enhanced hCMV IEG promoter (-548 to +92) activity in opossum kidney cells. Deletion analysis from the 5′ end of the promoter localized the PTH 1-84 associated activity to the DNA sequence between -123 and -45. Mutation of an imperfect ATF/AP-1 DNA element within this region abrogated the PTH 1-84 effect and also strongly attenuated basal gene expression. Mobility shift analyses using this DNA element revealed that a member of the ATF-1 family was in the binding complex. In summary, we present evidence for a novel pathogenic role of PTH 1-84 in promoting hCMV immediate-early gene transcription.

Original language	English
Pages (from-to)	977-982
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	368
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.02.019
State	Published - Apr 18 2008

Bibliographical note

Funding Information:
The authors thank H. Gravatte for her excellent technical assistance. This work was supported in part by the Kentucky Nephrology Research Trust, and University of Kentucky Medical Center Research Fund, Grant No. 1099992.

Funding

The authors thank H. Gravatte for her excellent technical assistance. This work was supported in part by the Kentucky Nephrology Research Trust, and University of Kentucky Medical Center Research Fund, Grant No. 1099992.

Funders	Funder number
Kentucky Nephrology Research Trust
University of Kentucky Medical Center Research Fund	1099992

Keywords

ATF-1
CREB
Chronic allograft nephropathy
DNA
Human cytomegalovirus
Immediate-early gene
Kidney
Parathyroid hormone
Transcription
Tubular cells

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.02.019

Cite this

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title = "PTH regulation of the human cytomegalovirus immediate-early gene promoter",

abstract = "Secondary hyperparathyroidism and human cytomegalovirus (hCMV) seropositivity are highly prevalent in patients undergoing renal transplantation, and both are linked to the development of chronic allograft nephropathy (CAN). We investigated the hypothesis that parathyroid hormone (PTH) 1-84 regulates hCMV immediate-early gene (IEG) promoter activation in proximal renal tubular cells. PTH 1-84 enhanced hCMV IEG promoter (-548 to +92) activity in opossum kidney cells. Deletion analysis from the 5′ end of the promoter localized the PTH 1-84 associated activity to the DNA sequence between -123 and -45. Mutation of an imperfect ATF/AP-1 DNA element within this region abrogated the PTH 1-84 effect and also strongly attenuated basal gene expression. Mobility shift analyses using this DNA element revealed that a member of the ATF-1 family was in the binding complex. In summary, we present evidence for a novel pathogenic role of PTH 1-84 in promoting hCMV immediate-early gene transcription.",

keywords = "ATF-1, CREB, Chronic allograft nephropathy, DNA, Human cytomegalovirus, Immediate-early gene, Kidney, Parathyroid hormone, Transcription, Tubular cells",

author = "Johann Herberth and Alimov, \{Alexander P.\} and Williams, \{John P.\} and Malluche, \{Hartmut H.\} and Koszewski, \{Nicholas J.\}",

note = "Funding Information: The authors thank H. Gravatte for her excellent technical assistance. This work was supported in part by the Kentucky Nephrology Research Trust, and University of Kentucky Medical Center Research Fund, Grant No. 1099992.",

year = "2008",

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language = "English",

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T1 - PTH regulation of the human cytomegalovirus immediate-early gene promoter

AU - Herberth, Johann

AU - Alimov, Alexander P.

AU - Williams, John P.

AU - Malluche, Hartmut H.

AU - Koszewski, Nicholas J.

N1 - Funding Information: The authors thank H. Gravatte for her excellent technical assistance. This work was supported in part by the Kentucky Nephrology Research Trust, and University of Kentucky Medical Center Research Fund, Grant No. 1099992.

PY - 2008/4/18

Y1 - 2008/4/18

N2 - Secondary hyperparathyroidism and human cytomegalovirus (hCMV) seropositivity are highly prevalent in patients undergoing renal transplantation, and both are linked to the development of chronic allograft nephropathy (CAN). We investigated the hypothesis that parathyroid hormone (PTH) 1-84 regulates hCMV immediate-early gene (IEG) promoter activation in proximal renal tubular cells. PTH 1-84 enhanced hCMV IEG promoter (-548 to +92) activity in opossum kidney cells. Deletion analysis from the 5′ end of the promoter localized the PTH 1-84 associated activity to the DNA sequence between -123 and -45. Mutation of an imperfect ATF/AP-1 DNA element within this region abrogated the PTH 1-84 effect and also strongly attenuated basal gene expression. Mobility shift analyses using this DNA element revealed that a member of the ATF-1 family was in the binding complex. In summary, we present evidence for a novel pathogenic role of PTH 1-84 in promoting hCMV immediate-early gene transcription.

AB - Secondary hyperparathyroidism and human cytomegalovirus (hCMV) seropositivity are highly prevalent in patients undergoing renal transplantation, and both are linked to the development of chronic allograft nephropathy (CAN). We investigated the hypothesis that parathyroid hormone (PTH) 1-84 regulates hCMV immediate-early gene (IEG) promoter activation in proximal renal tubular cells. PTH 1-84 enhanced hCMV IEG promoter (-548 to +92) activity in opossum kidney cells. Deletion analysis from the 5′ end of the promoter localized the PTH 1-84 associated activity to the DNA sequence between -123 and -45. Mutation of an imperfect ATF/AP-1 DNA element within this region abrogated the PTH 1-84 effect and also strongly attenuated basal gene expression. Mobility shift analyses using this DNA element revealed that a member of the ATF-1 family was in the binding complex. In summary, we present evidence for a novel pathogenic role of PTH 1-84 in promoting hCMV immediate-early gene transcription.

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KW - CREB

KW - Chronic allograft nephropathy

KW - DNA

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KW - Immediate-early gene

KW - Kidney

KW - Parathyroid hormone

KW - Transcription

KW - Tubular cells

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SN - 0006-291X

VL - 368

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JF - Biochemical and Biophysical Research Communications

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ER -

PTH regulation of the human cytomegalovirus immediate-early gene promoter

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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