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The Rat ARF Protein is Translated from Two Closely Spaced ATG Start Codons and Can Transcriptionally Activate p53 in the Absence of p53 Protein Stabilization
Abigail E. Hunt, Madeleine G. Moule and Mike Fried
volume 5 | issue 12
15 june 2006Pages: 1324 - 1330
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We have analyzed the transcriptional start sites of the rat ARF gene and the amino acid sequence of the rat ARF tumor suppressor protein. The 5' end of the rat ARF gene is similar to that of a number of cellular housekeeping genes in that it is CGrich and does not contain an upstream TATA box motif to define a precise transcriptional start site. The transcription of the rat ARF gene is initiated at multiple start sites with one major start site accounting for 41% of transcription. The rat ARF protein contains two methionine ATG codons at its amino terminus separated by 10 amino acids. The translation of the major endogenous ARF protein species is initiated from the upstream methionine ATG codon. The upstream methionine ATG codon is predominantly used, despite the fact that it is both very close to the major transcriptional start site (6 bases downstream) and is in a less favorable nucleic acid sequence context than the downstream ATG, relative to the ideal sequence postulated for efficient initiation of translation. The downstream, inefficient rat ARF ATG is equivalent to the major mouse ARF ATG start codon. Both of these closely spaced ATGs can be utilized as a translational start codon to produce a nucleolar-localized ARF protein which can induce a p53-dependent inhibition of cell division and transcriptional activation of p53 in the absence of p53 stabilization.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.