Cited by 72Cancer-related Molecular PathwaysGenomics and Chromatin DynamicsGene Regulatory Network Analysis

The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Open access
Tabach, Yuval, Milyavsky, Michael, Shats, Igor, Brosh, Ran, Zuk, Or, Yitzhaky, Assif, Mantovani, Roberto, Domany, Eytan +2 more·2005·Molecular Systems Biology

Abstract

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here, we analyzed genome-wide transcription profiling of an in vitro cancerous transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16(INK4A) tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16(INK4A), we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which, in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY, and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture, and activity of upstream signaling molecules.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/msb4100030

Cites

91 of 91 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Numerous cell cycle genes are downregulated via the p53-p21 pathway.

    “Following these reports, numerous cell cycle genes were found to be downregulated via the p53-p21 pathway.92, 93, 94, 95, 96, 97”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [93]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Tabach, Y., Milyavsky, M., Shats, I., Brosh, R., Zuk, O., Yitzhaky, A., Mantovani, R., Domany, E., Rotter, V., & Pilpel, Y.
Affiliations
  • Weizmann Institute of Science (IL)
  • University of Milan (IT)
Corresponding author
  • Rotter, Varda
  • Pilpel, Yitzhak
Venue
Molecular Systems Biology
Published
2005-10-18
Volume
1
Issue
1
Pages
2005.0022-2005.0022
ISSN
1744-4292 (ISSN-L)
OpenAlex
W2146032366
Cited by
72
References
90
Citations by year
2024: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 5
FWCI
2.49
Type
journal article
Language
en
Open access
Locations
  • Molecular Systems Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • arXiv (Cornell University)
Funders
  • Flight Attendant Medical Research Institute
  • Minerva Foundation
  • National Institutes of Health
  • National Cancer Institute (5 POI CA 65930-06, P01CA065930)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
cell cycle genes, promoter architecture, p53, p16INK4a, tumor suppressor inactivation, cell transformation, transcriptional repression, mitotic spindle, p21, NF-Y, E2F transcription factors, gene expression profiling, cancer signatures, proliferation rate
MeSH terms
Animals, Cell Division, Cell Line, Transformed, Cell Transformation, Neoplastic, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, Humans, Mice, Nude, Spindle Apparatus, Promoter Regions, Genetic, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Transplantation, Heterologous, Genes, Tumor Suppressor, Genes, p53, Tumor Suppressor Protein p53, Cell Cycle Proteins, Genes, cdc, Telomerase, Computational Biology, Cyclin-Dependent Kinase Inhibitor p16, Genes, p16, Gene Expression Profiling, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review