VprBP services two distinct E3 ubiquitin ligases. Some VprBP-interacting proteins are normally subjected to VprBP-dependent ubiquitination in unperturbed cells (native), whereas others are native or novel substrates that undergo accelerated Vpr- or Vpx-dependent degradation in the context of CRL4VprBP or EDD-Dyrk2DDB1-VprBP complexes. Merlin and UL35 may act to inhibit the CRL4 ligase. For several VprBP-interacting proteins, no evidence of ubiquitin modification has been reported. In some of these examples (e.g. mLgl2), the identity of the VprBP-associated E3 ligase has not been formally established. DDB1 may or may not physically link the EDD-Dyrk2 E3 ligase to substrates through VprBP in all cases. For additional details, see text.
Nakagawa et al. BMC Molecular Biology 2013 14:22 doi:10.1186/1471-2199-14-22