DNA microarrays identification of primary and secondary target genes regulated by p53.
Karuppiah Kannan,Ninette Amariglio,Gideon Rechavi,Jasmine Jakob-Hirsch,Itai Kela,Naftali Kaminski,Gad Getz,Eytan Domany,David Givol +8 more
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TLDR
The results suggest that p53 activates concerted opposing signals and exerts its effect through a diverse network of transcriptional changes that collectively alter the cell phenotype in response to stress.Abstract:
The transcriptional program regulated by the tumor suppressor p53 was analysed using oligonucleotide microarrays. A human lung cancer cell line that expresses the temperature sensitive murine p53 was utilized to quantitate mRNA levels of various genes at diAerent time points after shifting the temperature to 328C. Inhibition of protein synthesis by cycloheximide (CHX) was used to distinguish between primary and secondary target genes regulated by p53. In the absence of CHX, 259 and 125 genes were up or down-regulated respectively; only 38 and 24 of these genes were up and down-regulated by p53 also in the presence of CHX and are considered primary targets in this cell line. Cluster analysis of these data using the super paramagnetic clustering (SPC) algorithm demonstrate that the primary genes can be distinguished as a single cluster among a large pool of p53 regulated genes. This procedure identified additional genes that co-cluster with the primary targets and can also be classified as such genes. In addition to cell cycle (e.g. p21, TGF-b, Cyclin E) and apoptosis (e.g. Fas, Bak, IAP) related genes, the primary targets of p53 include genes involved in many aspects of cell function, including cell adhesion (e.g. Thymosin, Smoothelin), signaling (e.g. H-Ras, Diacylglycerol kinase), transcription (e.g. ATF3, LISCH7), neuronal growth (e.g. Ninjurin, NSCL2) and DNA repair (e.g. BTG2, DDB2). The results suggest that p53 activates concerted opposing signals and exerts its eAect through a diverse network of transcriptional changes that collectively alter the cell phenotype in response to stress. Oncogene (2001) 20, 2225‐2234.read more
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References
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p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
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Mdm2 promotes the rapid degradation of p53
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Tgfbeta signaling in growth control, cancer, and heritable disorders
TL;DR: The author would like to thank S. H. Roan for all her help and members of the Massague laboratory for insightful discussions.
Journal ArticleDOI
Definition of a consensus binding site for p53.
TL;DR: In this paper, a consensus binding site with a striking internal symmetry was identified, consisting of two copies of the 10 base pair motif 5′-PuPuC(A/T)(T/A)GPyPyPy-3′ separated by 0-13 base pairs.
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