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Tumor suppressor p53: a transcription elongation factor
Author(s) -
Balakrishnan Sri Kripa,
Gross David S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a287
Subject(s) - rna polymerase ii , transcription (linguistics) , biology , transcription factor , general transcription factor , microbiology and biotechnology , promoter , activator (genetics) , gene , transcription factor ii d , transcription factor ii f , genetics , transcriptional regulation , gene expression , linguistics , philosophy
Sequence‐specific transcriptional activators are normally thought to function by stably binding to their cognate DNA sequences, followed by recruitment of nucleosome remodeling complexes and components of the general transcription machinery to the promoter regions of target genes. We report evidence that the human tumor suppressor and sequence‐specific transcription activator p53, apart from binding to cognate binding sites, unexpectedly associates with the coding regions of transcriptionally active genes that are targets of RNA Polymerase II (Pol II) in vivo . p53's association with active genes is independent of its binding to the promoter and mutations within p53's core DNA binding domain or its C‐terminus does not obviate this association. Kinetic occupancy assays demonstrate that p53 travels with the elongating Pol II complex during transcription; in accordance, co‐immunoprecipitation experiments reveal that p53 physically interacts with Pol II. Furthermore, in the presence of the drug 6‐Azauracil, p53 + yeast cells elicit sickness and exhibit synthetic lethality in combination with mutations in various elongation factor genes. Thus, in addition to its known function as a sequence‐specific transcription activator, our work demonstrates that p53 can also function as a transcription elongation factor. Supported by the Feist Weiller Cancer Center, Shreveport, Louisiana.