Human Papillomavirus Type 16 E1
            <sup>∧</sup>
            E4-Induced G
            <sub>2</sub>
            Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes

Davy, Clare; Jackson, Deborah J.; Raj, Kenneth; Peh, Woei Ling; Southern, Shirley A.; Das, Papia; Sorathia, Rina; Laskey, Peter; Middleton, Kate; Nakahara, Tomomi; Wang, Qian; Masterson, Phillip J.; Lambert, Paul F.; Cuthill, Scott; Millar, Jonathan; Doorbar, John

doi:10.1128/jvi.79.7.3998-4011.2005

Cited by 73 publications

(78 citation statements)

References 44 publications

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“…Inhibiting the activation of the cdk1/cyclin B1 complex appears to be a common strategy used by both pathogenic viruses and bacteria to disrupt cell cycle progression (4,18,32,35). Interference with downstream events, including translocation of the active cdk1/cyclin B1 into the nucleus, has also been demonstrated for several viruses (6,30). Here we demonstrate that C. trachomatis may have evolved a separate mechanism to halt cell cycle progression by degrading cdk1 and targeting cyclin B1 for N-terminal truncation.…”

Section: Discussionmentioning

confidence: 99%

“…Altering the eukaryotic cell cycle actually appears to be an emerging theme for pathogens (33,38). Viruses such as human papillomavirus and human immunodeficiency virus are believed to halt cell cycle progression as a way of enhancing viral DNA replication and virus production (6,18,42). Similarly, it has been postulated that bacteria may induce host cell cycle arrest to aid their invasion and/or colonization (33).…”

Section: Discussionmentioning

confidence: 99%

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Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

et al. 2006

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The obligate intracellular pathogen Chlamydia trachomatis interferes with a number of host cell processes, including cytoskeletal organization, vesicular trafficking, and apoptosis. In this study we report that C. trachomatisinfected cells proliferate more slowly than uninfected cells, suggesting that C. trachomatis may also manipulate the eukaryotic cell cycle. We further demonstrate that C. trachomatis infection destabilizes specific cell cycle proteins involved in the G 2 /M transition. C. trachomatis-infected cells, compared to uninfected cells, have lower levels of cyclin-dependent kinase 1. Additionally, C. trachomatis infection induces an N-terminal truncation of the mitotic cyclin B1. Manipulation of the host cell cycle may represent a strategy used by C. trachomatis to ensure a stable environment conducive to bacterial growth and replication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

et al. 2006

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“…HIV can also utilize its Tat protein to stimulate the expression of cyclin B1, which is thought to promote apoptosis, and then to target cyclin B1 for proteasomal degradation by binding to the N terminus of cyclin B1 (40). The E4 protein of HPV16 is able to sequester the cyclin B1/CDK1 complex in the cytoplasm, thus preventing its nuclear localization and activity (41). In the studies presented here, we demonstrated that MVM uses a different approach to prevent the activation of the cyclin B1/CDK1 complex, by depleting both the cyclin B1 protein and, preceding that loss, the cyclin B1 RNA.…”

Section: Discussionmentioning

confidence: 99%

Minute Virus of Mice Inhibits Transcription of the Cyclin B1 Gene during Infection

Fuller

Majumder

Pintel

2017

J Virol

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Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus then exploits to prepare the nuclear environment for effective parvovirus takeover. An essential aspect of the MVMinduced DDR is the establishment of a potent premitotic block, which we previously found to be independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others reported previously, depends upon a significant, specific depletion of cyclin B1 and its encoding RNA, which precludes cyclin B1/CDK1 complex function, thus preventing mitotic entry. We show here that while the stability of cyclin B1 RNA was not affected by MVM infection, the production of nascent cyclin B1 RNA was substantially diminished at late times postinfection. Ectopic expression of NS1 alone did not reduce cyclin B1 expression. MVM infection also reduced the levels of cyclin B1 protein, and RNA levels normally increased in response to DNA-damaging reagents. We demonstrated that at times of reduced cyclin B1 expression during infection, there was a significantly reduced occupancy of RNA polymerase II and the essential mitotic transcription factor FoxM1 on the cyclin B1 gene promoter. Additionally, while total FoxM1 levels remained constant, there was a significant decrease of the phosphorylated, likely active, forms of FoxM1. Targeting of a constitutively active FoxM1 construct or the activation domain of FoxM1 to the cyclin B1 gene promoter via clustered regularly interspaced short palindromic repeats (CRISPR)-enzymatically inactive Cas9 in MVM-infected cells increased both cyclin B1 protein and RNA levels, implicating FoxM1 as a critical target for cyclin B1 inhibition during MVM infection.IMPORTANCE Replication of the parvovirus minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus exploits to prepare the nuclear environment for effective takeover. An essential aspect of the MVM-induced DDR is establishment of a potent premitotic block. This block depends upon a significant, specific depletion of cyclin B1 and its encoding RNA that precludes cyclin B1/CDK1 complex functions necessary for mitotic entry. We show that reduced cyclin B1 expression is controlled primarily at the level of transcription initiation. Additionally, the essential mitotic transcription factor FoxM1 and RNA polymerase II were found to occupy the cyclin B1 gene promoter at reduced levels during infection. Recruiting a constitutively active FoxM1 construct or the activation domain of FoxM1 to the cyclin B1 gene promoter via CRISPR-catalytically inactive Cas9 (dCas9) in MVM-infected cells increased expression of both cyclin B1 protein and RNA, implicating FoxM1 as a critical target mediating MVM-induced cyclin B1 inhibition.

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“…Instead, HBx persistently activated the cyclin B1-CDK1 kinase. The mechanism of G2/M arrest induced by other viral proteins is similar to that of G2/M arrest induced by HBx, such as human parvovirus B19 NS1 protein and human papillomavirus type 16 (HPV16) E1^E4 protein (13,20).…”

Section: Discussionmentioning

confidence: 77%

Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase

Cheng¹,

Li²,

Yang³

et al. 2009

Oncol Rep

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Abstract. Hepatitis B virus X protein (HBx) is a multifunctional regulatory protein that is known to be involved in viral proliferation, transcriptional activation and cell growth control. However, the actual role of HBx in cell growth control remains controversial. In this study, the impact of HBx on cell growth in vitro and in vivo was further investigated. HBx was able to inhibit the growth of hepatocellular carcinoma (HCC) cells and induce G2/M arrest in vitro. Moreover, unlike many other G2/M arrest mechanisms, HBx did not inhibit cyclin B1-CDK1 kinase activity, but it persistently activated the cyclin B1-CDK1 kinase. In vivo, HBx inhibited tumor cell growth and induced apoptosis as well as inhibited the growth of vascular endothelial cells. In conclusion, HBx induced G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase, and negatively regulated cell growth in vitro and in vivo.

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Human Papillomavirus Type 16 E1 ^∧ E4-Induced G ₂ Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes

Cited by 73 publications

References 44 publications

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

Minute Virus of Mice Inhibits Transcription of the Cyclin B1 Gene during Infection

Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase

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Human Papillomavirus Type 16 E1 ∧ E4-Induced G 2 Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes

Cited by 73 publications

References 44 publications

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

Minute Virus of Mice Inhibits Transcription of the Cyclin B1 Gene during Infection

Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase

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Human Papillomavirus Type 16 E1 ^∧ E4-Induced G ₂ Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes