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Co-immunoprecipitation and immunofluorescence assays demonstrated that HRD1 physically interacts with BMAL1 and enhances its K48-linked polyubiquitination, leading to proteasome-mediated degradation without altering BMAL1 mRNA levels (Mendoza-Viveros et al., 2017), and consistently, HRD1 overexpression significantly reduces PER1 and DBP mRNA levels, suggesting downstream transcriptional suppression via BMAL1 destabilization ( Drosophila ortholog of HDR1, called septin interacting protein 3 (sip3), in circadian regulation has not been identified

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