Coordination of transcription factors, NF-Y and C/EBPβ, in the regulation of the mdr1b promoter

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The expression of mdr genes that encode P-glycoprotein, an integral membrane drug transporter, has been associated with the emergence of the multidrug resistance phenotype during treatment with cancer chemotherapeutic drugs. To understand the regulation of the mdr genes, the murine mdr1b promoter has been isolated and characterized in our laboratory. Three nuclear protein binding sites that interact with nuclear proteins present in both drug-sensitive and -resistant murine macrophage-like J774.2 cells have been localized to the promoter. In this report, transcription factor NF-Y has been identified as binding to the Y-box sequence in site 1 and as a major factor in the regulation of the murine mdr1b promoter in the mouse adrenal cell line, Y-1, that endogenously expresses the mdr1b gene. The expression of CCAAT/enhancer binding protein β (C/EBPβ) in Y-1 cells augmented mdr1b promoter activity and resulted in an increased level of mdr1b mRNA. The effect of C/EBPβ expression on mdr1b promoter activity was sensitive to mutations in the Y-box, suggesting that coordination of NF-Y with C/EBPβ is required for further activation of the mdr1b promoter. Our studies have indicated that NF-Y is a critical factor for the mdr1b promoter, and its coordination with other factors, such as C/EBPβ, could be an important mechanism involved in mdr1b gene expression.

Original languageEnglish (US)
Pages (from-to)1505-1512
Number of pages8
JournalCell Growth and Differentiation
Volume6
Issue number12
StatePublished - 1995

Fingerprint

CCAAT-Enhancer-Binding Proteins
Transcription Factors
Nuclear Proteins
Pharmaceutical Preparations
Gene Expression
Membrane Transport Proteins
Multiple Drug Resistance
P-Glycoprotein
Protein Binding
Genes
Macrophages
Binding Sites
Phenotype
Cell Line
Messenger RNA
Mutation
Neoplasms

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

@article{9b1ced2156cf4c25b1f236739218de07,
title = "Coordination of transcription factors, NF-Y and C/EBPβ, in the regulation of the mdr1b promoter",
abstract = "The expression of mdr genes that encode P-glycoprotein, an integral membrane drug transporter, has been associated with the emergence of the multidrug resistance phenotype during treatment with cancer chemotherapeutic drugs. To understand the regulation of the mdr genes, the murine mdr1b promoter has been isolated and characterized in our laboratory. Three nuclear protein binding sites that interact with nuclear proteins present in both drug-sensitive and -resistant murine macrophage-like J774.2 cells have been localized to the promoter. In this report, transcription factor NF-Y has been identified as binding to the Y-box sequence in site 1 and as a major factor in the regulation of the murine mdr1b promoter in the mouse adrenal cell line, Y-1, that endogenously expresses the mdr1b gene. The expression of CCAAT/enhancer binding protein β (C/EBPβ) in Y-1 cells augmented mdr1b promoter activity and resulted in an increased level of mdr1b mRNA. The effect of C/EBPβ expression on mdr1b promoter activity was sensitive to mutations in the Y-box, suggesting that coordination of NF-Y with C/EBPβ is required for further activation of the mdr1b promoter. Our studies have indicated that NF-Y is a critical factor for the mdr1b promoter, and its coordination with other factors, such as C/EBPβ, could be an important mechanism involved in mdr1b gene expression.",
author = "L. Yu and Q. Wu and Yang, {Chia-Ping H.} and {Band Horwitz}, Susan",
year = "1995",
language = "English (US)",
volume = "6",
pages = "1505--1512",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Coordination of transcription factors, NF-Y and C/EBPβ, in the regulation of the mdr1b promoter

AU - Yu, L.

AU - Wu, Q.

AU - Yang, Chia-Ping H.

AU - Band Horwitz, Susan

PY - 1995

Y1 - 1995

N2 - The expression of mdr genes that encode P-glycoprotein, an integral membrane drug transporter, has been associated with the emergence of the multidrug resistance phenotype during treatment with cancer chemotherapeutic drugs. To understand the regulation of the mdr genes, the murine mdr1b promoter has been isolated and characterized in our laboratory. Three nuclear protein binding sites that interact with nuclear proteins present in both drug-sensitive and -resistant murine macrophage-like J774.2 cells have been localized to the promoter. In this report, transcription factor NF-Y has been identified as binding to the Y-box sequence in site 1 and as a major factor in the regulation of the murine mdr1b promoter in the mouse adrenal cell line, Y-1, that endogenously expresses the mdr1b gene. The expression of CCAAT/enhancer binding protein β (C/EBPβ) in Y-1 cells augmented mdr1b promoter activity and resulted in an increased level of mdr1b mRNA. The effect of C/EBPβ expression on mdr1b promoter activity was sensitive to mutations in the Y-box, suggesting that coordination of NF-Y with C/EBPβ is required for further activation of the mdr1b promoter. Our studies have indicated that NF-Y is a critical factor for the mdr1b promoter, and its coordination with other factors, such as C/EBPβ, could be an important mechanism involved in mdr1b gene expression.

AB - The expression of mdr genes that encode P-glycoprotein, an integral membrane drug transporter, has been associated with the emergence of the multidrug resistance phenotype during treatment with cancer chemotherapeutic drugs. To understand the regulation of the mdr genes, the murine mdr1b promoter has been isolated and characterized in our laboratory. Three nuclear protein binding sites that interact with nuclear proteins present in both drug-sensitive and -resistant murine macrophage-like J774.2 cells have been localized to the promoter. In this report, transcription factor NF-Y has been identified as binding to the Y-box sequence in site 1 and as a major factor in the regulation of the murine mdr1b promoter in the mouse adrenal cell line, Y-1, that endogenously expresses the mdr1b gene. The expression of CCAAT/enhancer binding protein β (C/EBPβ) in Y-1 cells augmented mdr1b promoter activity and resulted in an increased level of mdr1b mRNA. The effect of C/EBPβ expression on mdr1b promoter activity was sensitive to mutations in the Y-box, suggesting that coordination of NF-Y with C/EBPβ is required for further activation of the mdr1b promoter. Our studies have indicated that NF-Y is a critical factor for the mdr1b promoter, and its coordination with other factors, such as C/EBPβ, could be an important mechanism involved in mdr1b gene expression.

UR - http://www.scopus.com/inward/record.url?scp=0028826138&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028826138&partnerID=8YFLogxK

M3 - Article

C2 - 9019155

AN - SCOPUS:0028826138

VL - 6

SP - 1505

EP - 1512

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 12

ER -