Functioni
Core
component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3
ubiquitin-protein ligase complexes which mediate the ubiquitination and
subsequent proteasomal degradation of target proteins.
BCR complexes and
ARIH1 collaborate in tandem to mediate ubiquitination of target
proteins (PubMed:27565346).
As a scaffold protein may contribute to catalysis through positioning
of the substrate and the ubiquitin-conjugating enzyme. The E3
ubiquitin-protein ligase activity of the complex is dependent on the
neddylation of the cullin subunit and is inhibited by the association of
the deneddylated cullin subunit with TIP120A/CAND1.
The functional
specificity of the BCR complex depends on the BTB domain-containing
protein as the substrate recognition component. BCR(KLHL42) is involved
in ubiquitination of KATNA1.
BCR(SPOP) is involved in ubiquitination of
BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a
cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase
complex containing homodimeric SPOPL or the heterodimer formed by SPOP
and SPOPL; these complexes have lower ubiquitin ligase activity.
BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic
chromosomes and thereby coordinates faithful mitotic progression and
completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport
by regulating the size of COPII coats, thereby playing a key role in
collagen export, which is required for embryonic stem (ES) cells
division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31
(SEC31A or SEC31B) (PubMed:22358839,
PubMed:27716508).
BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762).
The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon
response and anterograde Golgi to endosome transport: it mediates both
ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination
(PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539).
The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of
the chromosomal passenger complex (CPC) from chromosomes to the spindle
midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937).
The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of
PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and
subsequent removal from kinetochores, allowing silencing of the spindle
assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478).
The BCR(KLHL22) ubiquitin ligase complex is also responsible for the
amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal
degradation of DEPDC5. Through the degradation of DEPDC5, releases the
GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719).
T
he BCR(KLHL25) ubiquitin ligase complex is involved in translational
homeostasis by mediating ubiquitination and subsequent degradation of
hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813).
The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1
and TCOF1, leading to remodel the translational program of
differentiating cells in favor of neural crest specification (PubMed:26399832).
Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus
involved in regulation of G1/S transition. Involved in the
ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046).
In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby
attenuating its ability to acetylate and activate ATM. The BCR(KCTD17)
E3 ubiquitin ligase complex mediates ubiquitination and degradation of
TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis
(PubMed:25270598).
The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of
KRT14, controls KRT14 levels during keratinocytes differentiation, and
is essential for skin integrity (PubMed:27798626).
The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination
of AURKA leading to its activation at the centrosome which is required
for initiating mitotic entry (PubMed:23213400).
The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of
oxidative and electrophilic stress* by mediating ubiquitination and
degradation of NFE2L2/NRF2, a transcription factor regulating expression
of many cytoprotective genes (PubMed:15601839, PubMed:16006525).30 Publications.
