ArticleJournal of virology2001
p21cip1 Degradation in differentiated keratinocytes is abrogated by costabilization with cyclin E induced by human papillomavirus E7.
Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis.Viruses · 2021Review
- Papillomaviruses and Endocytic Trafficking.International journal of molecular sciences · 2018Review
- HPV-Induced Field Cancerisation: Transformation of Adult Tissue Stem Cell Into Cancer Stem Cell.Frontiers in microbiology · 2018Article
- KDM6A addiction of cervical carcinoma cell lines is triggered by E7 and mediated by p21CIP1 suppression of replication stress.PLoS pathogens · 2017Article
- E6/E7 oncogenes in epithelial suprabasal layers and estradiol promote cervical growth and ear regeneration.Oncogenesis · 2017Article
- Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 Modulates Endocytic Cargo Transport Pathways.PLoS pathogens · 2016Article
- Increased sensitivity of HPV-positive head and neck cancer cell lines to x-irradiation ± Cisplatin due to decreased expression of E6 and E7 oncoproteins and enhanced apoptosis.American journal of cancer research · 2015Article
- Oncogenes and RNA splicing of human tumor viruses.Emerging microbes & infections · 2014Review
- Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses.Seminars in cancer biology · 2014Review
- Role of Cdk1 in DNA damage-induced G1 checkpoint abrogation by the human papillomavirus E7 oncogene.Cell cycle (Georgetown, Tex.) · 2014Article
- Human papillomavirus infections: warts or cancer?Cold Spring Harbor perspectives in biology · 2013Review
- HPV-18 E6 mutants reveal p53 modulation of viral DNA amplification in organotypic cultures.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- The human papillomavirus type 16 E7 oncoprotein targets Myc-interacting zinc-finger protein-1.Virology · 2012Article
- Human papillomavirus (HPV) E7 induces prolonged G2 following S phase reentry in differentiated human keratinocytes.The Journal of biological chemistry · 2011Article
- Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses.International journal of biological sciences · 2010Review
- Downregulation of Cdc2/CDK1 kinase activity induces the synthesis of noninfectious human papillomavirus type 31b virions in organotypic tissues exposed to benzo[a]pyrene.Journal of virology · 2010Article
- Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6.RNA (New York, N.Y.) · 2009Article
- E7 oncoprotein of novel human papillomavirus type 108 lacking the E6 gene induces dysplasia in organotypic keratinocyte cultures.Journal of virology · 2009Article
- The human papillomavirus E7 oncoprotein.Virology · 2009Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The human papillomavirus (HPV) E7 protein promotes S-phase reentry in a fraction of postmitotic, differentiated keratinocytes. Here we report that these cells contain an inherent mechanism that opposes E7-induced DNA replication. In organotypic raft cultures of primary human keratinocytes, neither cyclin E nor p21cip1 is detectable in situ. However, E7-transduced differentiated cells not in S phase accumulate abundant cyclin E and p21cip1. We show that normally p21cip1 protein is rapidly degraded by proteasomes. In the presence of E7 or E6/E7, p21cip1, cyclin E, and cyclin E2 proteins were all up-regulated. The accumulation of p21cip1 protein is a posttranscriptional event, and ectopic cyclin E expression was sufficient to trigger it. In constract, cdk2 and p27kip1 were abundant in normal differentiated cells and were not significantly affected by E7. Cyclin E, cdk2, and p21cip1 or p27kip1 formed complexes, and relatively little kinase activity was found associated with cyclin E or cdk2. In patient papillomas and E7 raft cultures, all p27kip1-positive cells were negative for bromodeoxyuridine (BrdU) incorporation, but only some also contained cyclin E and p21cip1. In contrast, all cyclin E-positive cells also contained p27kip1. When the expression of p21cip1 was reduced by rottlerin, a PKC delta inhibitor, p27kip1- and BrdU-positive cells remained unchanged. These observations show that high levels of endogenous p27kip1 can prevent E7-induced S-phase reentry. This inhibition then leads to the stabilization of cyclin E and p21cip1. Since efficient initiation of viral DNA replication requires cyclin E and cdk2, its inhibition accounts for heterogeneous viral activities in productively infected lesions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.