2011
DOI: 10.1074/jbc.m110.197574
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Human Papillomavirus (HPV) E7 Induces Prolonged G2 following S Phase Reentry in Differentiated Human Keratinocytes

Abstract: Human papillomaviruses (HPV)2 are small double-stranded DNA tumor viruses of considerable medical importance. They infect epithelial tissues, causing benign hyperproliferative lesions. More than 120 HPV genotypes have been cloned from patient specimens. The mucosotropic HPVs are broadly grouped into high-risk (HR) or low-risk (LR) types (1). Persistent infections of the cervix, penis, anus, and the oropharyngeal epithelium by HR HPV-16, HPV-18, and related types can at a low frequency progress into high grade … Show more

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Cited by 94 publications
(109 citation statements)
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References 55 publications
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“…1D). The treatment with the DNA damage agent is biologically relevant, as both E6 and E7 oncogenes from high-risk HPV types induce DNA damage and genomic instability (31)(32)(33). DNA damage may also result from spontaneous decay, replication errors, and cellular metabolism (34).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…1D). The treatment with the DNA damage agent is biologically relevant, as both E6 and E7 oncogenes from high-risk HPV types induce DNA damage and genomic instability (31)(32)(33). DNA damage may also result from spontaneous decay, replication errors, and cellular metabolism (34).…”
Section: Resultsmentioning
confidence: 99%
“…For example, the HPV-16 E4 protein prevents the nuclear entry of the mitotic cyclin/Cdk (48). In suprabasal cells, E7 expression induced cytoplasmic accumulation of cyclin B1 and Cdk1 with inactivating phosphorylation and G 2 arrest following S phase reentry (31). Arresting cells at G 2 may facilitate viral replication, as several viruses were found to replicate their genomes in the G 2 phase (49).…”
Section: Discussionmentioning
confidence: 99%
“…The expression of E7 stabilized p53 (17)(18)(19), which is attributable to E7 activation of DNA damage response kinases that not only phosphorylate p53 but also cause a prolonged G2 phase (32), during which the viral DNA amplifies (22). HPV missense E6 mutants destabilized the accumulated p53 much less effectively than the WT E6 (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…The epithelial portions of day 13 raft cultures were harvested and sonicated in mammalian cell lysis buffer supplemented with protease inhibitor mixture (Roche) as described (32); 200 μg lysates were Western-blotted. p53 antibody (DO7, 1:200 dilution; Novocastra), E6 antibody (2 μg/mL; Arbor Vita Corp), E7 antibody (N-19, 1:500 dilution; Santa Cruz), p21 antibody (1:1,000 dilution; Abcam), and β-actin antibody (mAbcam 8226, 1:7,000 dilution; Abcam) were used to probe the membranes.…”
Section: Methodsmentioning
confidence: 99%
“…Acting downstream of ATM and ATR are the Chk2 and Chk1 kinases, respectively, which phosphorylate a host of substrates to coordinate the DDR (30). Elements of both the ATM and ATR pathways are activated in HPV-positive cells, and a role for ATM activation has been implicated in productive HPV DNA replication (31)(32)(33)(34).…”
mentioning
confidence: 99%