Evidence map›Paper›PMID 12242284›Full record

ArticleMolecular and cellular biology2002

E7 abolishes raf-induced arrest via mislocalization of p21(Cip1).

Thomas F Westbrook, Don X Nguyen, Barry R Thrash, Dennis J McCance

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

32 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  18. Human papilloma virus (HPV) and host cellular interactions.Pathology oncology research : POR · 2008
    Review
  19. P21 and p27: roles in carcinogenesis and drug resistance.Expert reviews in molecular medicine · 2008
    Review
  20. Article
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.

Thomas F WestbrookDepartment of Microbiology and Immunology. Department of Biochemistry and Biophysics. The Cancer Center, University of Rochester, Rochester, New York 14642, USA.
Don X Nguyen
Barry R Thrash
Dennis J McCance
University of Rochester · US

Funding

Training in Microbial PathogenesisT32AI007362 · NIAID · UNIVERSITY OF ROCHESTER · PI IGLEWSKI, BARBARA H. · 1990 to 2010
$2.6M
HPV6 AND 16 EFFECTS ON EPITHELIAL CELL DIFFERENTIATIONR01AI030798 · NIAID · UNIVERSITY OF ROCHESTER · PI MCCANCE, DENNIS J. · 1990 to 2005
$1.6M
NIAID NIH HHS R01 AI030798NIAID NIH HHS R01AI30798NIAID NIH HHS T32AI07362
6 · The paper itself

Abstract

The cellular response to oncogenic Ras depends upon the presence or absence of cooperating mutations. In the absence of immortalizing oncogenes or genetic lesions, activation of the Ras/Raf pathway results in a p21(Cip1)-dependent cellular arrest. The human papillomavirus oncoprotein E7 transforms primary cells in cooperation with Ras and abolishes p21(Cip1)-mediated growth arrest in the presence of various antimitogenic signals. Here we have utilized a conditional Raf molecule to investigate the effects of E7 on p21(Cip1) function in the context of Raf-induced cellular arrest. E7 bypassed Raf-induced arrest and alleviated inhibition of cyclin E-CDK2 without suppressing Raf-specific synthesis of p21(Cip1) or derepressing p21(Cip1)-associated CDK2 complexes. Activation of Raf led to nuclear accumulation of p21(Cip1), and we provide evidence that this effect is mediated by inhibition of Akt, a regulator of p21(Cip1) localization. Loss of Akt activity appears to be an important event in the cellular arrest associated with Raf-induction, since maintenance of Akt activity was necessary and sufficient to bypass Raf-induced arrest. In agreement, expression of E7 sustained Akt activity and reduced nuclear accumulation of p21(Cip1), resulting in decreased association between p21(Cip1) and cyclin E-CDK2. Taken together, these data suggest that E7 inhibits p21(Cip1) function in the context of Raf signaling by altering Raf-Akt antagonism and preventing the proper subcellular localization of p21(Cip1). We propose that E7 elicits a proliferative response to Raf signaling by targeting p21(Cip1) function via a novel mechanism.

Indexed as

CDC2-CDC28 KinasesEnzyme Inhibitors3T3 CellsAnimalsCell DivisionCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclin ECyclinsHumansMiceOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPhosphatidylinositol 3-KinasesAKT1 protein, humanCDC2-CDC28 KinasesCDK2 protein, humanCdk2 protein, mouseCDKN1A protein, humanCdkn1a protein, mouseCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclin ECyclinsEnzyme Inhibitorsoncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-rafRecombinant Fusion Proteins

Identifiers

PMID12242284
PMCPMC139800
OpenAlexW2149228772

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.