Lytic replication-associated protein (RAP) encoded by Kaposi sarcoma-associated herpesvirus causes p21CIP-1-mediated G1 cell cycle arrest through CCAAT/enhancer-binding protein-α

Frederick Y. Wu, Qi Qun Tang, Honglin Chen, Colette ApRhys, Christopher Farrell, Jianmeng Chen, Masahiro Fujimuro, M. Daniel Lane, Gary Selwyn Hayward

Research output: Contribution to journalArticle

Abstract

Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes Kaposi sarcoma and AIDS-related primary effusion lymphoma (PEL). Here we show that KSHV lytic cycle replication in PEL cells induces G1 cell cycle arrest, presumably to facilitate the progression of viral DNA replication. Expression of a KSHV-encoded early lytic protein referred to as RAP or K8 is induced within 12-24 h after the onset of lytic cycle induction in host PEL cells, and coincides with increased levels of both the endogenous C/EBPα and p21CIP-1 proteins in the nucleus of the same cells. The KSHV RAP protein binds to C/EBPα in vitro and stimulates C/EBPα-induced expression from both the C/EBPα and p21 promoters in cotransfected cells. A recombinant adenovirus expressing the RAP protein induced the expression of both the C/EBPα and p21 proteins in primary human fibroblasts, and flow cytometric analysis revealed a dramatic inhibition of G1 to S cell cycle progression in the same cells. All of these effects were abolished in cells that lack C/EBPα or by deletion of the basic/leucine zipper region in RAP that interacts with C/EBPα. Therefore, C/EBPα is essential for the p21-mediated inhibition of G1 to S-phase progression by RAP in KSHV-infected host cells.

Original languageEnglish (US)
Pages (from-to)10683-10688
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number16
DOIs
StatePublished - Aug 2002

Fingerprint

CCAAT-Enhancer-Binding Proteins
G1 Phase Cell Cycle Checkpoints
Human Herpesvirus 8
Primary Effusion Lymphoma
Proteins
AIDS-Related Lymphoma
Leucine Zippers
Oncogenic Viruses
DNA Viruses
Kaposi's Sarcoma
Viral DNA
Cell Nucleus
DNA Replication
S Phase
Adenoviridae
Cell Cycle
Fibroblasts

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Lytic replication-associated protein (RAP) encoded by Kaposi sarcoma-associated herpesvirus causes p21CIP-1-mediated G1 cell cycle arrest through CCAAT/enhancer-binding protein-α. / Wu, Frederick Y.; Tang, Qi Qun; Chen, Honglin; ApRhys, Colette; Farrell, Christopher; Chen, Jianmeng; Fujimuro, Masahiro; Lane, M. Daniel; Hayward, Gary Selwyn.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 16, 08.2002, p. 10683-10688.

Research output: Contribution to journalArticle

Wu, Frederick Y. ; Tang, Qi Qun ; Chen, Honglin ; ApRhys, Colette ; Farrell, Christopher ; Chen, Jianmeng ; Fujimuro, Masahiro ; Lane, M. Daniel ; Hayward, Gary Selwyn. / Lytic replication-associated protein (RAP) encoded by Kaposi sarcoma-associated herpesvirus causes p21CIP-1-mediated G1 cell cycle arrest through CCAAT/enhancer-binding protein-α. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 16. pp. 10683-10688.
@article{5774071b95604e4fb6160e1387eda105,
title = "Lytic replication-associated protein (RAP) encoded by Kaposi sarcoma-associated herpesvirus causes p21CIP-1-mediated G1 cell cycle arrest through CCAAT/enhancer-binding protein-α",
abstract = "Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes Kaposi sarcoma and AIDS-related primary effusion lymphoma (PEL). Here we show that KSHV lytic cycle replication in PEL cells induces G1 cell cycle arrest, presumably to facilitate the progression of viral DNA replication. Expression of a KSHV-encoded early lytic protein referred to as RAP or K8 is induced within 12-24 h after the onset of lytic cycle induction in host PEL cells, and coincides with increased levels of both the endogenous C/EBPα and p21CIP-1 proteins in the nucleus of the same cells. The KSHV RAP protein binds to C/EBPα in vitro and stimulates C/EBPα-induced expression from both the C/EBPα and p21 promoters in cotransfected cells. A recombinant adenovirus expressing the RAP protein induced the expression of both the C/EBPα and p21 proteins in primary human fibroblasts, and flow cytometric analysis revealed a dramatic inhibition of G1 to S cell cycle progression in the same cells. All of these effects were abolished in cells that lack C/EBPα or by deletion of the basic/leucine zipper region in RAP that interacts with C/EBPα. Therefore, C/EBPα is essential for the p21-mediated inhibition of G1 to S-phase progression by RAP in KSHV-infected host cells.",
author = "Wu, {Frederick Y.} and Tang, {Qi Qun} and Honglin Chen and Colette ApRhys and Christopher Farrell and Jianmeng Chen and Masahiro Fujimuro and Lane, {M. Daniel} and Hayward, {Gary Selwyn}",
year = "2002",
month = "8",
doi = "10.1073/pnas.162352299",
language = "English (US)",
volume = "99",
pages = "10683--10688",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "16",

}

TY - JOUR

T1 - Lytic replication-associated protein (RAP) encoded by Kaposi sarcoma-associated herpesvirus causes p21CIP-1-mediated G1 cell cycle arrest through CCAAT/enhancer-binding protein-α

AU - Wu, Frederick Y.

AU - Tang, Qi Qun

AU - Chen, Honglin

AU - ApRhys, Colette

AU - Farrell, Christopher

AU - Chen, Jianmeng

AU - Fujimuro, Masahiro

AU - Lane, M. Daniel

AU - Hayward, Gary Selwyn

PY - 2002/8

Y1 - 2002/8

N2 - Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes Kaposi sarcoma and AIDS-related primary effusion lymphoma (PEL). Here we show that KSHV lytic cycle replication in PEL cells induces G1 cell cycle arrest, presumably to facilitate the progression of viral DNA replication. Expression of a KSHV-encoded early lytic protein referred to as RAP or K8 is induced within 12-24 h after the onset of lytic cycle induction in host PEL cells, and coincides with increased levels of both the endogenous C/EBPα and p21CIP-1 proteins in the nucleus of the same cells. The KSHV RAP protein binds to C/EBPα in vitro and stimulates C/EBPα-induced expression from both the C/EBPα and p21 promoters in cotransfected cells. A recombinant adenovirus expressing the RAP protein induced the expression of both the C/EBPα and p21 proteins in primary human fibroblasts, and flow cytometric analysis revealed a dramatic inhibition of G1 to S cell cycle progression in the same cells. All of these effects were abolished in cells that lack C/EBPα or by deletion of the basic/leucine zipper region in RAP that interacts with C/EBPα. Therefore, C/EBPα is essential for the p21-mediated inhibition of G1 to S-phase progression by RAP in KSHV-infected host cells.

AB - Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes Kaposi sarcoma and AIDS-related primary effusion lymphoma (PEL). Here we show that KSHV lytic cycle replication in PEL cells induces G1 cell cycle arrest, presumably to facilitate the progression of viral DNA replication. Expression of a KSHV-encoded early lytic protein referred to as RAP or K8 is induced within 12-24 h after the onset of lytic cycle induction in host PEL cells, and coincides with increased levels of both the endogenous C/EBPα and p21CIP-1 proteins in the nucleus of the same cells. The KSHV RAP protein binds to C/EBPα in vitro and stimulates C/EBPα-induced expression from both the C/EBPα and p21 promoters in cotransfected cells. A recombinant adenovirus expressing the RAP protein induced the expression of both the C/EBPα and p21 proteins in primary human fibroblasts, and flow cytometric analysis revealed a dramatic inhibition of G1 to S cell cycle progression in the same cells. All of these effects were abolished in cells that lack C/EBPα or by deletion of the basic/leucine zipper region in RAP that interacts with C/EBPα. Therefore, C/EBPα is essential for the p21-mediated inhibition of G1 to S-phase progression by RAP in KSHV-infected host cells.

UR - http://www.scopus.com/inward/record.url?scp=0036677565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036677565&partnerID=8YFLogxK

U2 - 10.1073/pnas.162352299

DO - 10.1073/pnas.162352299

M3 - Article

C2 - 12145325

AN - SCOPUS:0036677565

VL - 99

SP - 10683

EP - 10688

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 16

ER -