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Regulation of telomerase by human papillomaviruses.

Autor(es): Galloway, D A; Gewin, L C; Myers, H; Luo, W; Grandori, C; Katzenellenbogen, R A; McDougall, J K
Fonte: Cold Spring Harb Symp Quant Biol;70: 209-15, 2005.
Artigo [ PMID: 16869756 ] Idioma(s): Inglês
Publicação: Artigo de Revista; Research Support, N.I.H., Extramural
The E6 oncoprotein of human papillomaviruses (HPVs) induces telomerase activity in primary human epithelial cells. This activity is dependent on association of E6 with E6AP, a cellular ubiquitin ligase. E6 activates the transcription of hTERT, the catalytic subunit of telomerase. E boxes near the start of hTERT transcription are required for E6; however, acetylated histones are only present in the E6 cells. We identified two isoforms of NFX1, a new binding partner of E6/E6AP. The NFX1- 91 isoform binds to an X-box motif located adjacent to the proximal E box, binds Sin3A and HDACs, repressing hTERT transcription. It preferentially binds E6/E6AP and is targeted for ubiquitin-mediated degradation. The NFX1-123 isoform has the opposite activity, increasing hTERT transcription or translation. This is the first example of viral oncoproteins disrupting regulation of telomerase, a critical event in tumorigenesis.