Increased protein synthesis during cell proliferation is accompanied by a compensatory increase in efficient ribosome production, but the mechanisms by which cells adapt to this requirement are not fully understood. In the present study, we demonstrate evidence that Pygo (Pygopus), a protein originally identified as a core component of the Wnt–β-catenin transcription complex is also involved in rRNA transcription during cancer cell growth. Pygo was detected in the nucleoli of several transformed cell lines and was associated with treacle and UBF (upstream binding factor), proteins that are essential for ribosome biogenesis in development and cancer. Pygo was also detected at the ribosomal gene promoter along with core components of the rDNA (ribosomal DNA) transcription complex. RNAi (RNA interference)-mediated depletion of hPygo2 (human Pygo 2) reduced histone H4 acetylation at the rDNA promoter, down-regulated rRNA production, and induced growth arrest in both p53-positive and -negative cells. In p53-positive cells, hPygo2 knockdown triggered the ribosomal stress pathway, culminating in p53-dependent growth arrest at G1-phase of the cell cycle. The results of the present study suggest a novel involvement of Pygo in the promotion of rRNA transcription in cancer cells.

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