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Experimental activation of UBE3A achieved via expression of the HPV E6/E7 oncogenesin murine fibroblasts significantly disrupted circadian oscillations, reduced BMAL1 protein levels, and increased BMAL1 ubiquitination ( In Drosophila , both overexpression and knockdown of Ube3a in central clock neurons resulted in pronounced alterations in circadian locomotor rhythms, indicating that tight regulation of Ube3a levels is essential for proper pacemaker function across species (Wu et al., 2008)

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doi:10.1038/176325a0