v-erbA acts receptors on retinoic acid receptors in immature avian erythroid cells

Stephen Sande, Mohammed Sharif, Hongwu Chen, Martin Privalsky

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes an aberrant version of a gene for a thyroid hormone receptor (c-erbA) and functions in neoplasia by blocking erythroid differentiation and altering the growth properties of fibroblasts. The v-erbA gene has been proposed to act as a dominant negative allele, functioning by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. The v-erbA protein can also, however, interfere with the actions of other members of the nuclear hormone receptor family, and it has been proposed that interference with a retinoic acid-mediated response may be a crucial determinant of v-erbA's function in the cancer cell. Here we report that the ability of v-erbA to interfere with retinoic acid receptor (RAR) action extends to the neoplastic erythroid cell and that v-erbA can inhibit transcriptional activation by all three isoforms (α, β, and γ) of RAR. Overexpression of RAR-α was found to partially overcome the presumptive v-erbA block to transcription in the erythroleukemic cell. These results are consistent with our hypothesis that v-erbA can act in neoplasia by interfering with a retinoic acid-mediated signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)1067-1074
Number of pages8
JournalJournal of Virology
Volume67
Issue number2
StatePublished - Feb 1993

Fingerprint

Erythroid Cells
Retinoic Acid Receptors
erbA Genes
retinoic acid
Thyroid Hormone Receptors
immatures
Tretinoin
Oncogene Proteins v-erbA
receptors
Alpharetrovirus
Neoplasms
Avian erythroblastosis virus
cells
Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Signal Transduction
Protein Isoforms
Fibroblasts
Alleles
neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

v-erbA acts receptors on retinoic acid receptors in immature avian erythroid cells. / Sande, Stephen; Sharif, Mohammed; Chen, Hongwu; Privalsky, Martin.

In: Journal of Virology, Vol. 67, No. 2, 02.1993, p. 1067-1074.

Research output: Contribution to journalArticle

Sande, S, Sharif, M, Chen, H & Privalsky, M 1993, 'v-erbA acts receptors on retinoic acid receptors in immature avian erythroid cells', Journal of Virology, vol. 67, no. 2, pp. 1067-1074.
Sande, Stephen ; Sharif, Mohammed ; Chen, Hongwu ; Privalsky, Martin. / v-erbA acts receptors on retinoic acid receptors in immature avian erythroid cells. In: Journal of Virology. 1993 ; Vol. 67, No. 2. pp. 1067-1074.
@article{355705b0f82e44b5bc969c417af865f7,
title = "v-erbA acts receptors on retinoic acid receptors in immature avian erythroid cells",
abstract = "The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes an aberrant version of a gene for a thyroid hormone receptor (c-erbA) and functions in neoplasia by blocking erythroid differentiation and altering the growth properties of fibroblasts. The v-erbA gene has been proposed to act as a dominant negative allele, functioning by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. The v-erbA protein can also, however, interfere with the actions of other members of the nuclear hormone receptor family, and it has been proposed that interference with a retinoic acid-mediated response may be a crucial determinant of v-erbA's function in the cancer cell. Here we report that the ability of v-erbA to interfere with retinoic acid receptor (RAR) action extends to the neoplastic erythroid cell and that v-erbA can inhibit transcriptional activation by all three isoforms (α, β, and γ) of RAR. Overexpression of RAR-α was found to partially overcome the presumptive v-erbA block to transcription in the erythroleukemic cell. These results are consistent with our hypothesis that v-erbA can act in neoplasia by interfering with a retinoic acid-mediated signal transduction pathway.",
author = "Stephen Sande and Mohammed Sharif and Hongwu Chen and Martin Privalsky",
year = "1993",
month = "2",
language = "English (US)",
volume = "67",
pages = "1067--1074",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - v-erbA acts receptors on retinoic acid receptors in immature avian erythroid cells

AU - Sande, Stephen

AU - Sharif, Mohammed

AU - Chen, Hongwu

AU - Privalsky, Martin

PY - 1993/2

Y1 - 1993/2

N2 - The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes an aberrant version of a gene for a thyroid hormone receptor (c-erbA) and functions in neoplasia by blocking erythroid differentiation and altering the growth properties of fibroblasts. The v-erbA gene has been proposed to act as a dominant negative allele, functioning by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. The v-erbA protein can also, however, interfere with the actions of other members of the nuclear hormone receptor family, and it has been proposed that interference with a retinoic acid-mediated response may be a crucial determinant of v-erbA's function in the cancer cell. Here we report that the ability of v-erbA to interfere with retinoic acid receptor (RAR) action extends to the neoplastic erythroid cell and that v-erbA can inhibit transcriptional activation by all three isoforms (α, β, and γ) of RAR. Overexpression of RAR-α was found to partially overcome the presumptive v-erbA block to transcription in the erythroleukemic cell. These results are consistent with our hypothesis that v-erbA can act in neoplasia by interfering with a retinoic acid-mediated signal transduction pathway.

AB - The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes an aberrant version of a gene for a thyroid hormone receptor (c-erbA) and functions in neoplasia by blocking erythroid differentiation and altering the growth properties of fibroblasts. The v-erbA gene has been proposed to act as a dominant negative allele, functioning by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. The v-erbA protein can also, however, interfere with the actions of other members of the nuclear hormone receptor family, and it has been proposed that interference with a retinoic acid-mediated response may be a crucial determinant of v-erbA's function in the cancer cell. Here we report that the ability of v-erbA to interfere with retinoic acid receptor (RAR) action extends to the neoplastic erythroid cell and that v-erbA can inhibit transcriptional activation by all three isoforms (α, β, and γ) of RAR. Overexpression of RAR-α was found to partially overcome the presumptive v-erbA block to transcription in the erythroleukemic cell. These results are consistent with our hypothesis that v-erbA can act in neoplasia by interfering with a retinoic acid-mediated signal transduction pathway.

UR - http://www.scopus.com/inward/record.url?scp=0027393961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027393961&partnerID=8YFLogxK

M3 - Article

C2 - 8093487

AN - SCOPUS:0027393961

VL - 67

SP - 1067

EP - 1074

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -