UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 ...

created [InstanceEdit:8955259] Rothfels, Karen, 2017-01-10
dbId 8955258
displayName UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 ...
modified [InstanceEdit:9766982] Rothfels, Karen, 2022-02-24
schemaClass Summation
text UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 and 4 (Huang et al, 2009; Monda et al, 2013). Interaction between UBE2M and the CUL3 E3 complex is facilitated by a DCUN1D (also known as DCNL) scaffold protein, of which there are 5 in human cells (Kim et al, 2008; Kurz et al, 2008; Meyer-Schaller et al, 2009; Monda et al, 2013; Keuss et al, 2016). DCUN1D proteins interact with higher affinity to the N-terminally acetylated forms of UBE2F and UBE2M (Scott et al, 2011; Monda et al, 2013). Although each of the 5 DCUN1D proteins appears to interact with most cullin subtypes, specificity may arise through differences in expression and localization, and DCUN1D3 may play a specialized role in sequestering CRL E3 ligase complexes at the cell membrane (Monda et al, 2013; Keuss et al, 2016; Meyer-Schaller et al, 2009; Huang et al, 2014; reviewed in Enchev et al, 2103). Although in this pathway, COMMD proteins and DCUN1D are shown acting sequentially in the activation of the CRL E3 ligase complex, the relationship between these protein families is not totally clear, as DCUN1D proteins have been identified in complexes that also contain the inhibitor CAND1 (Kim et al, 2008; Huang et al, 2014).
Target specificity of the CRL3 complex is directed by the nature of the BTB substrate recognition protein. For instance, BTB protein KEAP1 is the main controller of NFE2L2 stability (Cuadrado et al, 2019). CRL3 complexes target proteins involved in processes such as development and stress response (reviewed in Genschik et al, 2013). CRL3 complexes are also hijacked by a number of viruses, redirecting the ubiquitin ligase complex to target host proteins and in this way promoting viral propagation (reviewed in Mahon et al, 2014).
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