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Initially identified as a CRY1-interacting protein in a high-throughput yeast two-hybrid screen (Rual et al., 2005), TRAF2 was later shown to bind directly to BMAL1, reducing its abundance without affecting CRY1 levels ( TRAF2 overexpression enhances BMAL1 ubiquitination and proteasomal degradation, thereby attenuating E-box-mediated transcription and dampening PER1 oscillations ( 4.1.18 UBE3A UBE3A, an E3 ubiquitin ligase previously implicated in Angelman syndrome and HPV-related tumorigenesis, has recently emerged as a conserved regulator of the circadian clock through its post-translational control of BMAL1 stability (Mabb et al., 2011)