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Table 2 Characterized PTMs occurring on BubR1

From: Physiological relevance of post-translational regulation of the spindle assembly checkpoint protein BubR1

Modification Residue Added by Reversed by Mechanism Functional consequences Mutational consequences References
Phosphorylation T608 BubR1 (auto)
Plk1?
PP1? Unknown—acts on Aurora B kinase Polar chromosome migration
SAC reinforcement
Deficient: reduced Aurora B-mediated KMN phosphorylation, attachment errors [59]
T620 Cdk1 PP2A-B56, PP1-Knl1 Docking site for Plk1 KC-MT stability Deficient: defective KC-MT attachments, prolonged mitotic arrest [28, 46]
S670 Cdk1
Mps1?
Other?
PP1-Knl1 Recruit PP2A-B56 KC-MT stability (attachment sensitive) Deficient: loss of tension downstream?
High incidence of lagging chromosomes
Chromosome alignment defects
[42, 43, 113]
S676 Plk1 PP1-Knl1 Recruit PP2A-B56 KC-MT stability (tension sensitive) Deficient: chromosome alignment defects [28, 37, 45, 113]
T680 Plk1 PP1-Knl1 Recruit PP2A-B56 KC-MT stability (tension sensitive) Deficient: chromosome alignment defects [37, 45, 113]
T792 Plk1 Unknown Unknown BubR1 kinase activity
KC-MT stability
Deficient: decreased BubR1 autophosphorylation
Mimetic: Increased BubR1 autophosphorylation
[43, 73]
T1008 Plk1 Unknown Unknown BubR1 kinase activity
KC-MT stability
Deficient: decreased BubR1 phosphorylation
Mimetic: increased BubR1 phosphorylation
[43, 73]
S1043 Mps1
Cdk1?
Unknown Unknown Unknown (attachment sensitive, PTM patterns resemble S670) [43]
Acetylation K250 PCAF HDAC2/3
SIRT2
Protect BubR1 from premature degradation during mitosis by blocking APC/C MCC stability, anaphase inhibition
Chromosome migration
K250R (deficient): accelerated mitosis, missegregation of chromosomes
K250Q (mimetic): delayed chromosome segregation following alignment
[86, 88,89,90]
K668 CBP SIRT2 Signal ubiquitination machinery BubR1 ubiquitination, degradation during interphase Deficient: Increased BubR1 abundance [87]
Ubiquitination Unknown Cdc20-APC/C Unknown Target BubR1 to proteasome Dissociation of MCC
BubR1 degradation
[101, 102]
SUMOylation K250 Unknown
RanBP2
SUMO E3 ligase?
Unknown Dissociation of BubR1 from kinetochore; association with CENP-E; facilitate BubR1-Sgo1 interaction; BubR1 degradation? BubR1 degradation? SAC silencing (checkpoint inactivation)
Timely and complete chromosome segregation
Deficient: BubR1 retained on kinetochores,
anaphase delay and premature chromatid separation
[106, 108]