Human tumor suppressor p14ARF negatively regulates rRNA transcription and inhibits UBF1 transcription factor phosphorylation.

The nucleolar Arf protein has been shown to regulate cell cycle through both p53-dependent and -independent pathways. In addition to the well-characterized Arf-mdm2-p53 pathway, several partners of Arf have recently been described that could participate in alternative regulation process. Among those is the nucleolar protein B23/NPM, involved in the sequential maturation of rRNA. p19ARF can interact with B23/NPM in high molecular complexes and partially inhibit the cleavage of the 32S rRNA, whereas the human p14ARF protein has been shown to participate in the degradation of NPM/B23 by the proteasome. These data led to define Arf as a negative regulator of ribosomal RNA maturation. Our recent finding that the human p14ARF protein was able to specifically interact with the rRNA promoter in a p53-independent context, led us to analyse in vitro and in vivo the consequences of this interaction. Luciferase assay and pulse-chase experiments demonstrated that the rRNA transcription was strongly reduced upon p14ARF overexpression. Investigations on potential interactions between p14ARF and the transcription machinery proteins demonstrated that the upstream binding factor (UBF), required for the initiation of the transcriptional complex, was a new partner of the p14ARF protein. We next examined the phosphorylation status of UBF as UBF phosphorylation is required to recruit on the promoter factors involved in the transcriptional complex. Upon p14ARF overexpression, UBF was found hypophosphorylated, thus unable to efficiently recruit the transcription complex. Taken together, these data define a new p53-independent pathway that could regulate cell cycle through the negative control of rRNA transcription.

[Double contrast barium enema-colonoscopy. Comparative diagnostic value in 73 patients (author's transl)]. / Lavement baryté en double contraste-coloscopie. Valeur diagnostique comparée chez 73 malades.

Double contrast barium enema and colonoscopy are great value in the diagnosis of lesions of the colon, especially polyps. This study involved 73 patients. The results were in agreement in 71,2% of cases and disagreed in 23,3%. In 5,5%, colonoscopy was technically inadequate. Classical barium enema remains indicated for the detection of carcinoma or in elderly or bedridden individuals. By contrast, barium enema should be replaced by double contrast study in the aetiological evaluation of rectal bleeding. In our own series, the diagnosis was positive in 92% of cases as long as both the radiological and endoscopic techniques were used.