The human cytomegalovirus IE1-72 protein interacts with the cellular p107 protein and relieves p107-mediated transcriptional repression of an E2F- responsive promoter

Eric E. Poma, Timothy F. Kowalik, Liang Zhu, John H. Sinclair, Eng Shang Huang

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

The Rb-related p107 protein has been implicated as an important control element in proper cell cycle progression. The p107 protein is thought to restrict cellular proliferation in part through its interaction with the E2F family of transcription factors and is, therefore, a specific target for regulation by several DNA viruses. Here, we demonstrate that p107 protein levels are induced in a biphasic manner in human fibroblasts during productive infection by the human cytomegalovirus (HCMV). Expression patterns of p107 protein levels during HCMV infection of human embryonic lung cells (HELs) demonstrate a sustained induction from early to late times of infection. We also demonstrate that the HCMV immediate-early protein IE1-72 complexes in vivo with the p107 protein and that this interaction can be reconstituted in an in vitro system by using reticulocyte-translated protein. Our data demonstrate that the interaction between p107 and the IE1-72 protein occurs at times of infection that temporally match the second tier of p107 protein induction and the phosphorylation pattern of the IE1-72 protein. Furthermore, we show here that the ability of p107 in transcriptionally repress E2F-responsive promoters can be overcome by expression of the IE1-72 protein. This effect appears to be specific, since the IE1-72 protein is not capable of relieving Rb-mediated repression of an E2F-responsive promoter. Finally, our data demonstrate that HCMV infection can induce cellular proliferation in quiescent cells and that IE1-72 expression alone can, to a degree, drive a similar progression through the cell cycle. These data suggest that IE1-72-mediated transactivation of E2F-responsive promoters through alleviation of p107 transcriptional repression may play a key role in the cell cycle progression stimulated by HCMV infection.

Original languageEnglish (US)
Pages (from-to)7867-7877
Number of pages11
JournalJournal of Virology
Volume70
Issue number11
StatePublished - Nov 1996
Externally publishedYes

Fingerprint

Human herpesvirus 5
promoter regions
Proteins
Cytomegalovirus Infections
proteins
Cell Cycle
cell cycle
cytomegalovirus IE1 protein
cell proliferation
Cell Proliferation
E2F Transcription Factors
infection
DNA Viruses
DNA viruses
reticulocytes
Reticulocytes
Infection
transcriptional activation
Transcriptional Activation
fibroblasts

ASJC Scopus subject areas

  • Immunology

Cite this

The human cytomegalovirus IE1-72 protein interacts with the cellular p107 protein and relieves p107-mediated transcriptional repression of an E2F- responsive promoter. / Poma, Eric E.; Kowalik, Timothy F.; Zhu, Liang; Sinclair, John H.; Huang, Eng Shang.

In: Journal of Virology, Vol. 70, No. 11, 11.1996, p. 7867-7877.

Research output: Contribution to journalArticle

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