Proliferative activation of quiescent rat-1A cells by ΔFosB

Yusaku Nakabeppu, S. Oda, M. Sekiguchi

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that ΔFosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although ΔFosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of ΔFosB transforms Rat-1A cells as does expression of FosB. The transforming ability of ΔFosB suggests that ΔFosB may lead to proliferative activation of quiescent cells without activating AP-1- responsive genes. To address this question, FosB or ΔFosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-ΔFosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-ΔFosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N- terminal region and the DNA binding domain of FosB or ΔFosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.

Original languageEnglish
Pages (from-to)4157-4166
Number of pages10
JournalMolecular and Cellular Biology
Volume13
Issue number7
Publication statusPublished - Jan 1 1993

Fingerprint

Estrogen Receptors
Matrix Metalloproteinase 3
Transcription Factor AP-1
Transcriptional Activation
Proteins
Serum
DNA Replication
Cell Division
Genes
Intercellular Signaling Peptides and Proteins
Estrogens
Transcription Factors
Cell Proliferation
Ligands
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Proliferative activation of quiescent rat-1A cells by ΔFosB. / Nakabeppu, Yusaku; Oda, S.; Sekiguchi, M.

In: Molecular and Cellular Biology, Vol. 13, No. 7, 01.01.1993, p. 4157-4166.

Research output: Contribution to journalArticle

Nakabeppu, Yusaku ; Oda, S. ; Sekiguchi, M. / Proliferative activation of quiescent rat-1A cells by ΔFosB. In: Molecular and Cellular Biology. 1993 ; Vol. 13, No. 7. pp. 4157-4166.
@article{441b1459a2d24549b46aa77e28a49a1a,
title = "Proliferative activation of quiescent rat-1A cells by ΔFosB",
abstract = "Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that ΔFosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although ΔFosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of ΔFosB transforms Rat-1A cells as does expression of FosB. The transforming ability of ΔFosB suggests that ΔFosB may lead to proliferative activation of quiescent cells without activating AP-1- responsive genes. To address this question, FosB or ΔFosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-ΔFosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-ΔFosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N- terminal region and the DNA binding domain of FosB or ΔFosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.",
author = "Yusaku Nakabeppu and S. Oda and M. Sekiguchi",
year = "1993",
month = "1",
day = "1",
language = "English",
volume = "13",
pages = "4157--4166",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Proliferative activation of quiescent rat-1A cells by ΔFosB

AU - Nakabeppu, Yusaku

AU - Oda, S.

AU - Sekiguchi, M.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that ΔFosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although ΔFosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of ΔFosB transforms Rat-1A cells as does expression of FosB. The transforming ability of ΔFosB suggests that ΔFosB may lead to proliferative activation of quiescent cells without activating AP-1- responsive genes. To address this question, FosB or ΔFosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-ΔFosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-ΔFosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N- terminal region and the DNA binding domain of FosB or ΔFosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.

AB - Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that ΔFosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although ΔFosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of ΔFosB transforms Rat-1A cells as does expression of FosB. The transforming ability of ΔFosB suggests that ΔFosB may lead to proliferative activation of quiescent cells without activating AP-1- responsive genes. To address this question, FosB or ΔFosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-ΔFosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-ΔFosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N- terminal region and the DNA binding domain of FosB or ΔFosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.

UR - http://www.scopus.com/inward/record.url?scp=0027310172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027310172&partnerID=8YFLogxK

M3 - Article

C2 - 8321220

AN - SCOPUS:0027310172

VL - 13

SP - 4157

EP - 4166

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -