Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein.

M Mannervik; S Fan; A C Ström; K Helin; G Akusjärvi

doi:10.1006/viro.1999.9663

Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein.

M Mannervik, S Fan, A C Ström, K Helin, G Akusjärvi

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

27 Citationer (Scopus)

Abstract

Udgivelsesdato: 1999-Apr-10

Originalsprog	Engelsk
Tidsskrift	Virology
Vol/bind	256
Udgave nummer	2
Sider (fra-til)	313-21
Antal sider	8
ISSN	0042-6822
DOI	https://doi.org/10.1006/viro.1999.9663
Status	Udgivet - 1999

Bibliografisk note

Adgang til dokumentet

10.1006/viro.1999.9663

Citationsformater

Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein. / Mannervik, M; Fan, S; Ström, A C et al.
I: Virology, Bind 256, Nr. 2, 1999, s. 313-21.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{7570cc2053dc11dd8d9f000ea68e967b,

title = "Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein.",

abstract = "Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression during virus growth. E4-ORF4 has previously been shown to bind to and activate the cellular protein phosphatase 2A. The inhibitory effect of E4-ORF4 was relieved by okadaic acid, which inhibits protein phosphatase 2A activity, suggesting that E4-ORF4 represses E2 transcription by inducing transcription factor dephosphorylation. Interestingly, E4-ORF4 did not inhibit the transactivation capacity of a Gal4-E2F hybrid protein. Instead, E4-ORF4 expression appears to result in reduced stability of E2F/DNA complexes.",

author = "M Mannervik and S Fan and Str{\"o}m, {A C} and K Helin and G Akusj{\"a}rvi",

note = "Keywords: Adenovirus E1A Proteins; Adenovirus E2 Proteins; Adenovirus E4 Proteins; Binding Sites; Carrier Proteins; Cell Cycle Proteins; DNA-Binding Proteins; Dimerization; Drosophila Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Gene Expression Regulation, Viral; Hela Cells; Humans; Open Reading Frames; Phosphorylation; Promoter Regions (Genetics); RNA, Messenger; Retinoblastoma Protein; Trans-Activation (Genetics); Trans-Activators; Transcription Factor DP1; Transcription Factors; Tumor Cells, Cultured",

year = "1999",

doi = "10.1006/viro.1999.9663",

language = "English",

volume = "256",

pages = "313--21",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press",

number = "2",

}

TY - JOUR

T1 - Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein.

AU - Mannervik, M

AU - Fan, S

AU - Ström, A C

AU - Helin, K

AU - Akusjärvi, G

N1 - Keywords: Adenovirus E1A Proteins; Adenovirus E2 Proteins; Adenovirus E4 Proteins; Binding Sites; Carrier Proteins; Cell Cycle Proteins; DNA-Binding Proteins; Dimerization; Drosophila Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Gene Expression Regulation, Viral; Hela Cells; Humans; Open Reading Frames; Phosphorylation; Promoter Regions (Genetics); RNA, Messenger; Retinoblastoma Protein; Trans-Activation (Genetics); Trans-Activators; Transcription Factor DP1; Transcription Factors; Tumor Cells, Cultured

PY - 1999

Y1 - 1999

N2 - Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression during virus growth. E4-ORF4 has previously been shown to bind to and activate the cellular protein phosphatase 2A. The inhibitory effect of E4-ORF4 was relieved by okadaic acid, which inhibits protein phosphatase 2A activity, suggesting that E4-ORF4 represses E2 transcription by inducing transcription factor dephosphorylation. Interestingly, E4-ORF4 did not inhibit the transactivation capacity of a Gal4-E2F hybrid protein. Instead, E4-ORF4 expression appears to result in reduced stability of E2F/DNA complexes.

AB - Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression during virus growth. E4-ORF4 has previously been shown to bind to and activate the cellular protein phosphatase 2A. The inhibitory effect of E4-ORF4 was relieved by okadaic acid, which inhibits protein phosphatase 2A activity, suggesting that E4-ORF4 represses E2 transcription by inducing transcription factor dephosphorylation. Interestingly, E4-ORF4 did not inhibit the transactivation capacity of a Gal4-E2F hybrid protein. Instead, E4-ORF4 expression appears to result in reduced stability of E2F/DNA complexes.

U2 - 10.1006/viro.1999.9663

DO - 10.1006/viro.1999.9663

M3 - Journal article

C2 - 10191196

SN - 0042-6822

VL - 256

SP - 313

EP - 321

JO - Virology

JF - Virology

IS - 2

ER -