Table 2 Characterized PTMs occurring on 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 | ||
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 | ||
S676 | Plk1 | PP1-Knl1 | Recruit PP2A-B56 | KC-MT stability (tension sensitive) | Deficient: chromosome alignment defects | ||
T680 | Plk1 | PP1-Knl1 | Recruit PP2A-B56 | KC-MT stability (tension sensitive) | Deficient: chromosome alignment defects | ||
T792 | Plk1 | Unknown | Unknown | BubR1 kinase activity KC-MT stability | Deficient: decreased BubR1 autophosphorylation Mimetic: Increased BubR1 autophosphorylation | ||
T1008 | Plk1 | Unknown | Unknown | BubR1 kinase activity KC-MT stability | Deficient: decreased BubR1 phosphorylation Mimetic: increased BubR1 phosphorylation | ||
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 | |
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 | – | |
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 |