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

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dc.creatorTabach, Yuval
dc.creatorMilyavsky, Michael
dc.creatorShats, Igor
dc.creatorBrosh, Ran
dc.creatorZuk, Or
dc.creatorYitzhaky, Assif
dc.creatorMantovani, Roberto
dc.creatorDomany, Eytan
dc.creatorPilpel, Varda Rotter Yitzhak
dc.date2005-11-15
dc.date.accessioned2026-07-07T06:52:34Z
dc.date.available2026-07-07T06:52:34Z
dc.descriptionDeciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A 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 p16INK4A, 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.
dc.descriptionTo appear in Molecular Systems Biology
dc.identifierhttps://arxiv.org/abs/q-bio/0511022
dc.identifierhttp://arxiv.org/abs/q-bio/0511022
dc.identifier.urihttp://salesiana.dossiersoluciones.com/handle/123456789/105342
dc.subjectMolecular Networks
dc.subjectQuantitative Methods
dc.titleThe promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation
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