The transcriptional repressor, ZFM1 interacts with and modulates the ability of EWS to activate transcription

Di Zhang, Ari J. Paley, Geoffrey J. Childs

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

The ZFM1 protein is both a transcriptional repressor and identical to the splicing factor SF1. ZFM1 was shown to interact with and repress transcription from the glycine, glutamine, serine, and threonine-rich transcription activation domain of the sea urchin transcription factor, stage-specific activator protein (SSAP). EWS, a human protein involved in cellular transformation in Ewing's sarcoma tumors, contains an NH2-terminal transcriptional activation domain (NTD) which resembles that of SSAP in both amino acid composition and the ability to drive transcription to levels higher than VP16 in most cell types. Here we report that ZFM1 also interacts with EWS in both two-hybrid assays and glutathione S-transferase pull-down experiments. The region on EWS which interacts with ZFM1 maps to 37 amino acids within its NTD. Overexpression of ZFM1 in HepG2 cells represses the transactivation of reporter gene expression driven by Gal4-EWS-NTD fusion protein and this repression correlates with ZFM1 binding to EWS. Furthermore, two proteins, TLS and hTAF(II)68, which have extensive homology to EWS, also interact with ZFM1. Recently, it was discovered that EWS/TLS/hTAF(II)68 are each present in distinct TFIID populations and EWS and hTAF(II)68 were also found to be associated with the RNA polymerase II holoenzyme. The association of ZFM1 with these proteins implies that one normal cellular function for ZFM1 may be to negatively modulate transcription of target genes coordinated by these cofactors.

Original languageEnglish (US)
Pages (from-to)18086-18091
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number29
DOIs
StatePublished - Jul 17 1998

Fingerprint

Transcription
Transcriptional Activation
Chemical activation
Ewing's Sarcoma
Proteins
RNA-Binding Protein FUS
Transcription Factor TFIID
Amino Acids
Holoenzymes
Two-Hybrid System Techniques
Sea Urchins
RNA Polymerase II
Hep G2 Cells
Threonine
Glutathione Transferase
Glutamine
Reporter Genes
Glycine
Serine
Gene expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

The transcriptional repressor, ZFM1 interacts with and modulates the ability of EWS to activate transcription. / Zhang, Di; Paley, Ari J.; Childs, Geoffrey J.

In: Journal of Biological Chemistry, Vol. 273, No. 29, 17.07.1998, p. 18086-18091.

Research output: Contribution to journalArticle

@article{919834a4ae12474194fa6ae794fb1fca,
title = "The transcriptional repressor, ZFM1 interacts with and modulates the ability of EWS to activate transcription",
abstract = "The ZFM1 protein is both a transcriptional repressor and identical to the splicing factor SF1. ZFM1 was shown to interact with and repress transcription from the glycine, glutamine, serine, and threonine-rich transcription activation domain of the sea urchin transcription factor, stage-specific activator protein (SSAP). EWS, a human protein involved in cellular transformation in Ewing's sarcoma tumors, contains an NH2-terminal transcriptional activation domain (NTD) which resembles that of SSAP in both amino acid composition and the ability to drive transcription to levels higher than VP16 in most cell types. Here we report that ZFM1 also interacts with EWS in both two-hybrid assays and glutathione S-transferase pull-down experiments. The region on EWS which interacts with ZFM1 maps to 37 amino acids within its NTD. Overexpression of ZFM1 in HepG2 cells represses the transactivation of reporter gene expression driven by Gal4-EWS-NTD fusion protein and this repression correlates with ZFM1 binding to EWS. Furthermore, two proteins, TLS and hTAF(II)68, which have extensive homology to EWS, also interact with ZFM1. Recently, it was discovered that EWS/TLS/hTAF(II)68 are each present in distinct TFIID populations and EWS and hTAF(II)68 were also found to be associated with the RNA polymerase II holoenzyme. The association of ZFM1 with these proteins implies that one normal cellular function for ZFM1 may be to negatively modulate transcription of target genes coordinated by these cofactors.",
author = "Di Zhang and Paley, {Ari J.} and Childs, {Geoffrey J.}",
year = "1998",
month = "7",
day = "17",
doi = "10.1074/jbc.273.29.18086",
language = "English (US)",
volume = "273",
pages = "18086--18091",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

TY - JOUR

T1 - The transcriptional repressor, ZFM1 interacts with and modulates the ability of EWS to activate transcription

AU - Zhang, Di

AU - Paley, Ari J.

AU - Childs, Geoffrey J.

PY - 1998/7/17

Y1 - 1998/7/17

N2 - The ZFM1 protein is both a transcriptional repressor and identical to the splicing factor SF1. ZFM1 was shown to interact with and repress transcription from the glycine, glutamine, serine, and threonine-rich transcription activation domain of the sea urchin transcription factor, stage-specific activator protein (SSAP). EWS, a human protein involved in cellular transformation in Ewing's sarcoma tumors, contains an NH2-terminal transcriptional activation domain (NTD) which resembles that of SSAP in both amino acid composition and the ability to drive transcription to levels higher than VP16 in most cell types. Here we report that ZFM1 also interacts with EWS in both two-hybrid assays and glutathione S-transferase pull-down experiments. The region on EWS which interacts with ZFM1 maps to 37 amino acids within its NTD. Overexpression of ZFM1 in HepG2 cells represses the transactivation of reporter gene expression driven by Gal4-EWS-NTD fusion protein and this repression correlates with ZFM1 binding to EWS. Furthermore, two proteins, TLS and hTAF(II)68, which have extensive homology to EWS, also interact with ZFM1. Recently, it was discovered that EWS/TLS/hTAF(II)68 are each present in distinct TFIID populations and EWS and hTAF(II)68 were also found to be associated with the RNA polymerase II holoenzyme. The association of ZFM1 with these proteins implies that one normal cellular function for ZFM1 may be to negatively modulate transcription of target genes coordinated by these cofactors.

AB - The ZFM1 protein is both a transcriptional repressor and identical to the splicing factor SF1. ZFM1 was shown to interact with and repress transcription from the glycine, glutamine, serine, and threonine-rich transcription activation domain of the sea urchin transcription factor, stage-specific activator protein (SSAP). EWS, a human protein involved in cellular transformation in Ewing's sarcoma tumors, contains an NH2-terminal transcriptional activation domain (NTD) which resembles that of SSAP in both amino acid composition and the ability to drive transcription to levels higher than VP16 in most cell types. Here we report that ZFM1 also interacts with EWS in both two-hybrid assays and glutathione S-transferase pull-down experiments. The region on EWS which interacts with ZFM1 maps to 37 amino acids within its NTD. Overexpression of ZFM1 in HepG2 cells represses the transactivation of reporter gene expression driven by Gal4-EWS-NTD fusion protein and this repression correlates with ZFM1 binding to EWS. Furthermore, two proteins, TLS and hTAF(II)68, which have extensive homology to EWS, also interact with ZFM1. Recently, it was discovered that EWS/TLS/hTAF(II)68 are each present in distinct TFIID populations and EWS and hTAF(II)68 were also found to be associated with the RNA polymerase II holoenzyme. The association of ZFM1 with these proteins implies that one normal cellular function for ZFM1 may be to negatively modulate transcription of target genes coordinated by these cofactors.

UR - http://www.scopus.com/inward/record.url?scp=0032541042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032541042&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.29.18086

DO - 10.1074/jbc.273.29.18086

M3 - Article

C2 - 9660765

AN - SCOPUS:0032541042

VL - 273

SP - 18086

EP - 18091

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -