Transactivation activity of Meq, a Marek's disease herpesvirus bZIP protein persistently expressed in latently infected transformed T cells

Z. Qian, P. Brunovskis, F. Rauscher, L. Lee, H. J. Kung

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Marek's disease virus (MDV) is an avian herpesvirus that induces a variety of diseases, including T-cell lymphomas, in chickens. In latently infected, transformed lymphoid cells, very few viral transcripts or proteins are detected. We previously described a gene, meq (MDV EcoQ), which is persistently expressed in MDV-transformed tumor samples and cell lines. meq codes for a 339-amino-acid protein with a basic-leucine zipper domain near its N terminus and a proline-rich domain near its C terminus. The basic- leucine zipper domain shows homology with Jun/Fos family proteins, whereas the proline-rich domain resembles that of the WT-1 tumor suppressor protein. These structural features raise the possibility that Meq functions as a transcription factor in regulating vital latency or oncogenesis. In this report, we show that the proline-rich domain is a potent: transcription activator when fused to the yeast (Saccharomyces cerevisiae) Gal4(1-147) DNA- binding domain. The transactivation activity maps to the C-terminal 130 amino acids, with the last 33 amino acids essential. In the absence of these 33 amino acids, a two-and-one-half proline-rich repeat structure was found to exhibit repression activity. We further show that Meq is able to dimerize not only with itself but also with c-Jun. Meq/c-Jun heterodimers bind to an AP1- like sequence in the meq promoter region with an affinity much greater than that of Meq/Meq or c-Jun/c-Jun homodimers. Cotransfection chloramphenicol acetyltransferase assays suggest that the Meq/c-Jun heterodimers can up- regulate Meq expression in both chicken embryo fibroblasts and F9 cells. Our data provide the first biochemical evidence that Meq is a transcriptional factor and identify c-Jun as one of Meq's interacting partners.

Original languageEnglish
Pages (from-to)4037-4044
Number of pages8
JournalJournal of Virology
Volume69
Issue number7
Publication statusPublished - Jan 1 1995
Externally publishedYes

Fingerprint

Basic-Leucine Zipper Transcription Factors
Marek Disease
Marek disease
Herpesviridae
transcriptional activation
Proline
Mardivirus
Transcriptional Activation
proline
Leucine Zippers
T-lymphocytes
Viruses
T-Lymphocytes
Proline-Rich Protein Domains
Amino Acids
leucine zipper
Chickens
amino acids
Tumor Suppressor Proteins
Transformed Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Transactivation activity of Meq, a Marek's disease herpesvirus bZIP protein persistently expressed in latently infected transformed T cells. / Qian, Z.; Brunovskis, P.; Rauscher, F.; Lee, L.; Kung, H. J.

In: Journal of Virology, Vol. 69, No. 7, 01.01.1995, p. 4037-4044.

Research output: Contribution to journalArticle

@article{38113145a5e14d839eff2578b47b7c41,
title = "Transactivation activity of Meq, a Marek's disease herpesvirus bZIP protein persistently expressed in latently infected transformed T cells",
abstract = "Marek's disease virus (MDV) is an avian herpesvirus that induces a variety of diseases, including T-cell lymphomas, in chickens. In latently infected, transformed lymphoid cells, very few viral transcripts or proteins are detected. We previously described a gene, meq (MDV EcoQ), which is persistently expressed in MDV-transformed tumor samples and cell lines. meq codes for a 339-amino-acid protein with a basic-leucine zipper domain near its N terminus and a proline-rich domain near its C terminus. The basic- leucine zipper domain shows homology with Jun/Fos family proteins, whereas the proline-rich domain resembles that of the WT-1 tumor suppressor protein. These structural features raise the possibility that Meq functions as a transcription factor in regulating vital latency or oncogenesis. In this report, we show that the proline-rich domain is a potent: transcription activator when fused to the yeast (Saccharomyces cerevisiae) Gal4(1-147) DNA- binding domain. The transactivation activity maps to the C-terminal 130 amino acids, with the last 33 amino acids essential. In the absence of these 33 amino acids, a two-and-one-half proline-rich repeat structure was found to exhibit repression activity. We further show that Meq is able to dimerize not only with itself but also with c-Jun. Meq/c-Jun heterodimers bind to an AP1- like sequence in the meq promoter region with an affinity much greater than that of Meq/Meq or c-Jun/c-Jun homodimers. Cotransfection chloramphenicol acetyltransferase assays suggest that the Meq/c-Jun heterodimers can up- regulate Meq expression in both chicken embryo fibroblasts and F9 cells. Our data provide the first biochemical evidence that Meq is a transcriptional factor and identify c-Jun as one of Meq's interacting partners.",
author = "Z. Qian and P. Brunovskis and F. Rauscher and L. Lee and Kung, {H. J.}",
year = "1995",
month = "1",
day = "1",
language = "English",
volume = "69",
pages = "4037--4044",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Transactivation activity of Meq, a Marek's disease herpesvirus bZIP protein persistently expressed in latently infected transformed T cells

AU - Qian, Z.

AU - Brunovskis, P.

AU - Rauscher, F.

AU - Lee, L.

AU - Kung, H. J.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Marek's disease virus (MDV) is an avian herpesvirus that induces a variety of diseases, including T-cell lymphomas, in chickens. In latently infected, transformed lymphoid cells, very few viral transcripts or proteins are detected. We previously described a gene, meq (MDV EcoQ), which is persistently expressed in MDV-transformed tumor samples and cell lines. meq codes for a 339-amino-acid protein with a basic-leucine zipper domain near its N terminus and a proline-rich domain near its C terminus. The basic- leucine zipper domain shows homology with Jun/Fos family proteins, whereas the proline-rich domain resembles that of the WT-1 tumor suppressor protein. These structural features raise the possibility that Meq functions as a transcription factor in regulating vital latency or oncogenesis. In this report, we show that the proline-rich domain is a potent: transcription activator when fused to the yeast (Saccharomyces cerevisiae) Gal4(1-147) DNA- binding domain. The transactivation activity maps to the C-terminal 130 amino acids, with the last 33 amino acids essential. In the absence of these 33 amino acids, a two-and-one-half proline-rich repeat structure was found to exhibit repression activity. We further show that Meq is able to dimerize not only with itself but also with c-Jun. Meq/c-Jun heterodimers bind to an AP1- like sequence in the meq promoter region with an affinity much greater than that of Meq/Meq or c-Jun/c-Jun homodimers. Cotransfection chloramphenicol acetyltransferase assays suggest that the Meq/c-Jun heterodimers can up- regulate Meq expression in both chicken embryo fibroblasts and F9 cells. Our data provide the first biochemical evidence that Meq is a transcriptional factor and identify c-Jun as one of Meq's interacting partners.

AB - Marek's disease virus (MDV) is an avian herpesvirus that induces a variety of diseases, including T-cell lymphomas, in chickens. In latently infected, transformed lymphoid cells, very few viral transcripts or proteins are detected. We previously described a gene, meq (MDV EcoQ), which is persistently expressed in MDV-transformed tumor samples and cell lines. meq codes for a 339-amino-acid protein with a basic-leucine zipper domain near its N terminus and a proline-rich domain near its C terminus. The basic- leucine zipper domain shows homology with Jun/Fos family proteins, whereas the proline-rich domain resembles that of the WT-1 tumor suppressor protein. These structural features raise the possibility that Meq functions as a transcription factor in regulating vital latency or oncogenesis. In this report, we show that the proline-rich domain is a potent: transcription activator when fused to the yeast (Saccharomyces cerevisiae) Gal4(1-147) DNA- binding domain. The transactivation activity maps to the C-terminal 130 amino acids, with the last 33 amino acids essential. In the absence of these 33 amino acids, a two-and-one-half proline-rich repeat structure was found to exhibit repression activity. We further show that Meq is able to dimerize not only with itself but also with c-Jun. Meq/c-Jun heterodimers bind to an AP1- like sequence in the meq promoter region with an affinity much greater than that of Meq/Meq or c-Jun/c-Jun homodimers. Cotransfection chloramphenicol acetyltransferase assays suggest that the Meq/c-Jun heterodimers can up- regulate Meq expression in both chicken embryo fibroblasts and F9 cells. Our data provide the first biochemical evidence that Meq is a transcriptional factor and identify c-Jun as one of Meq's interacting partners.

UR - http://www.scopus.com/inward/record.url?scp=0029046226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029046226&partnerID=8YFLogxK

M3 - Article

VL - 69

SP - 4037

EP - 4044

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 7

ER -