Evidence map›Paper›PMID 11390614›Full record

ArticleJournal of virology2001

p21cip1 Degradation in differentiated keratinocytes is abrogated by costabilization with cyclin E induced by human papillomavirus E7.

F Noya, W M Chien, T R Broker, L T Chow

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Papillomaviruses and Endocytic Trafficking.International journal of molecular sciences · 2018
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Oncogenes and RNA splicing of human tumor viruses.Emerging microbes & infections · 2014
    Review
  9. Review
  10. Article
  11. Human papillomavirus infections: warts or cancer?Cold Spring Harbor perspectives in biology · 2013
    Review
  12. 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 · 2013
    Article
  13. Article
  14. Article
  15. Article
  16. Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses.International journal of biological sciences · 2010
    Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

F NoyaDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
W M Chien
T R Broker
L T Chow
University of Alabama at Birmingham · US

Funding

HUMAN PAPILLOMAVIRUS GENE EXPRESSIONR01CA036200 · NCI · UNIVERSITY OF ROCHESTER · PI BROKER, THOMAS R · 1985 to 2003
$1.4M
ROLE OF NUTRITIONAL AND OTHER FACTORS IN ETIOLOGY OF ORAL CANCERP50DE011910 · NIDCR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SOONG, SENG-JAW T. · 1996 to 2001
$987k
NCI NIH HHS CA36200NCI NIH HHS R01 CA036200NIDCR NIH HHS DE/CA 11910
6 · The paper itself

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.

Indexed as

DNA-Binding ProteinsAcetophenonesAcetylcysteineAnimalsBenzopyransCyclin-Dependent Kinase Inhibitor p21Cyclin ECyclinsCysteine EndopeptidasesHumansInfant, NewbornKeratinocytesMultienzyme ComplexesOncogene Proteins, ViralProteasome Endopeptidase ComplexProtein Kinase CAcetophenonesAcetylcysteineBenzopyransCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21Cyclin ECyclinsCysteine EndopeptidasesDNA-Binding ProteinsE7 protein, Human papillomavirus type 18lactacystinMultienzyme ComplexesOncogene Proteins, ViralProteasome Endopeptidase ComplexProtein Kinase Crottlerin

Identifiers

PMID11390614
PMCPMC114328
OpenAlexW2149979695

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.