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Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.
Gene References into Functions
Human gastric cancer tissues with low BUBR1 expression showed no eNOS expression. A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation. PMID: 30396924
Authors show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. PMID: 27457023
we found that FOXM1 inhibitor attenuated tumorigenesis and radioresistance of glioblastoma (GBM) both in vitro and in vivo. Altogether, BUB1B promotes tumor proliferation and induces radioresistance in GBM, indicating that BUB1B could be a potential therapeutic target for GBM. PMID: 29039578
Results from phylogenomic study identified of a novel conserved cassette of short linear motifs in BubR1 essential for the spindle checkpoint PMID: 28003474
BubR1 N-terminal domain was necessary, but not sufficient to protect against aneuploidy and cancer. In contrast, BubR1 lacking the internal Cdc20-binding domain provided protection against both, which coincided with improved microtubule-kinetochore attachment error correction and spindle assembly checkpoint activity. PMID: 27528194
Low BUB1B expression is associated with Chromophobe Renal Cell Carcinomas. PMID: 28807937
Whether carriers of pathogenic BUB1B mutations, such as the parents of MVA syndrome patients, have an increased risk for cancer remains of interest, as studies in mice have suggested that haploinsufficiency of BUB1B may cause an increase in carcinogen-induced tumors PMID: 27239782
structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets. PMID: 27350047
Overexpression of BUB1B is associated with Invasive Breast Cancer. PMID: 27165245
we showed that BubR1 and Mad2 are overexpressed in oral squamous cell carcinoma cell lines and linked such overexpression to attenuated spindle assembly checkpoint activity. We also showed BubR1 overexpression to be associated with advanced stage and tumour size. PMID: 25754611
The integrity of the mitotic checkpoint complex depends on the specific recognition between BubR1 and Bub3, for which the BubR1 Gle2 binding sequence motif is essential. PMID: 27030009
We show that kinetochore recruitment of BUBR1 and BUB3 by BUB1 is dispensable for SAC activation PMID: 26148513
Data suggest that both BubR1 and SNCG may be promising predictive marker rather than prognostic marker in patients with breast cancer. PMID: 26191236
BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. PMID: 26151845
BubR1 contributes to preventing premature aging. [review] PMID: 25964054
Suggest human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy in HPV-induced cervical cancer. PMID: 25789401
In conclusion, the results presented here suggest that Mad2 and BubR1 could be used as prognostic markers of tumor progression and new pharmacological targets in the treatment for gastric cancer . PMID: 25483095
Co-depletion of MAD2 and BUBR1 causes cell cycle arrest and cell death in addition to aneuploidy. PMID: 24687487
By sequestering PIDD at the kinetochore, BubR1 acts to delay PIDDosome formation until the next cycle, defining a new mechanism by which cells evade apoptosis during mitosis. PMID: 25936804
a Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing PMID: 25482201
study shows that SIRT2 is a deacetylase for BubR1 K250, although the abnormally prolonged SAC activation observed in SIRT2 knockdown cells is not accompanied by a change in BubR1 levels or by delayed progression from prometaphase to anaphase PMID: 25285631
YAP constitutively associated with BubR1 (BUB1-related protein kinase), and knockdown of BubR1 relieved YAP-driven hyperactivation of the spindle checkpoint. PMID: 25605730
Data indicate that cell cycle protein Bub3-mediated kinetochore recruitment of BubR1 kinase enhances mitotic checkpoint signaling. PMID: 25246557
the BubR1M-Cdc20 interaction indirectly contributes to mitotic checkpoint complex homeostasis PMID: 25505175
The ABBA motif in cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20 PMID: 25669885
Our findings indicated an interplay between BUBR1 and p53 in colorectal cancer. Altered expression of both molecules was associated with chromosomal instability. PMID: 25275037
the loss of BubR1 levels with age is due to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP. PMID: 24825348
In acute myeloid leukemia, repression of BubR1 is associated with enhanced anaphase-promoting complex activity. PMID: 23812934
p53 deficiency may lead to the failure of BubR1 downregulation by OS and that p53 deficiency and BubR1 accumulation could contribute to gastric carcinogenesis associated with aneuploidy. PMID: 24156017
BubR1 overexpression was associated with cell proliferation and may play a role in the carcinogenesis of gastrointestinal diffuse large B cell lymphoma PMID: 23400934
These results suggest that the malignant transformation of plexiform neurofibroma is associated with distinct changes in the expression of BUB1B, PBK and NEK2 PMID: 23370767
High levels of BubR1 were less sensitive to the anti-microtubule drugs paclitaxel and nocodazole in esophageal squamous cell carcinoma. PMID: 23128493
Data suggest that BubR1 counteracts Aurora B kinase activity at improperly attached kinetochores by recruiting B56-PP2A phosphatase complexes. PMID: 23345399
Reduced BubR1 expression is strongly associated with longer survival in prostate cancer patients. PMID: 23475578
Mad2 Binding Induces a Functional Switch in Cdc20,Enabling BubR1 Binding. PMID: 23791783
findings highlight the insufficiency of BUB1 haploinsufficiency to directly stimulate tumourigenesis, and suggest that other factors may be more critical to this process. PMID: 23440991
Rsf-1 increases the frequency of abnormal mitotic events by disrupting hBubR1-Cdc20 interactions. PMID: 23536579
Results suggest that targeting the GLEBS domain activity of BUB1B may provide a therapeutic window for glioblastoma. PMID: 23154965
Elevated BUBR1 expression was associated with poor survival in early stage breast cancer patients PMID: 23392733
The PLK1 and BUBR1 cooperate to stabilize kinetochore-microtubule interactions by regulating PP2A-B56alpha-mediated dephosphorylation of Aurora B substrates at the kinetochore-microtubule interface. PMID: 23079597
It was shown that the state of CENP-E-dependent BubR1 autophosphorylation in response to spindle microtubule capture by CENP-E is important for kinetochore function in achieving accurate chromosome segregation. PMID: 22801780
Results reveal that BubR1 sumoylation plays an important role in its timely removal from the kinetochores and the checkpoint inactivation, thus allowing normal anaphase entry and chromosome segregation. PMID: 22374677
It was shown that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution. It was also shown that putative catalysis by human BUBR1 is dispensable for error-free chromosome segregation. PMID: 22698286
p31(comet) negatively regulates the spindle assembly checkpoint by extracting Mad2 from the MCC. PMID: 22100920
a new type of post-translational modification that is essential for BubR1 function during mitosis. PMID: 22167194
we identify the Blinkin motif critical for interaction with BUBR1, define the stoichiometry and affinity of the interaction, and present a 2.2 Angstrom resolution crystal structure of the complex PMID: 22000412
DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. PMID: 22048964
Aging-related loss of BubR1 and subsequent impairment of reactivity to reactive oxygen species may explain reduced proliferative capacity of aged smooth muscle cells. PMID: 21550059
Our data imply the possibility that BUBR1 may be involved in the progression of oral squamous cell carcinoma, and suggest that BUBR1 may be a promising prognostic marker in patients with OSCC PMID: 21069850
BUBR1 and closed MAD2 (C-MAD2) interact directly to assemble a functional mitotic checkpoint complex PMID: 21525009
Cytoplasm. Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Cytoplasmic in interphase cells. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and KNL1.
Protein Families
Protein kinase superfamily, Ser/Thr protein kinase family, BUB1 subfamily
Tissue Specificity
Highly expressed in thymus followed by spleen. Preferentially expressed in tissues with a high mitotic index.