BUB1

Official Full Name

BUB1 mitotic checkpoint serine/threonine kinase

Organism

Homo sapiens

GeneID

699

Background

This gene encodes a serine/threonine-protein kinase that play a central role in mitosis. The encoded protein functions in part by phosphorylating members of the mitotic checkpoint complex and activating the spindle checkpoint. This protein also plays a role in inhibiting the activation of the anaphase promoting complex/cyclosome. This protein may also function in the DNA damage response. Mutations in this gene have been associated with aneuploidy and several forms of cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Synonyms

BUB1A; BUB1L; hBUB1; MCPH30;

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Detailed Information

Recent Research Progress

Benzimidazole 1 (BUB1) is a mitotic checkpoint serine/threonine kinase that plays a key role in cell division and maintenance of chromosomal stability. During mitosis, BUB1 plays several roles, such as recruitment of mitotic checkpoint proteins to kinetochore, installation of mitotic checkpoint responses and chromosome convergence. BUB1 has several protein-protein interaction domains, such as the tetraploid repeat (TPR), GLE2p-binding sequence (GLEBS) and conserved region (CDI) domains involved in recruiting the mitotic checkpoint proteins to the kinetochore and the spindle checkpoint function, and Ser/Thr kinase domain involved in chromosome congression. It is reported that any errors in these processes or domains can lead to tumorigenesis.

BUB1 and breast cancer

Breast cancer is the leading cause of death among women worldwide due to treatment resistance and cancer recurrence. Cancer stem cells are thought to be responsible for resistance and recurrence. Many efforts to overcome drug resistance and relapse by modulating cancer stem cells are ongoing. Recently, studies have shown that BUB1 expression is associated with poor clinical outcomes in breast cancer patients. Studies have shown that consumption of BUB1 using short hairpin RNA (shRNA) reduces the cancer stem cell potential of the MDA-MB-231 breast cancer cell line, resulting in inhibition of xenograft formation in immunocompromised mice. These results suggest that BUB1 may be associated with cancer stem cell potential and may be the target for the development of anti-breast cancer stem cell therapies.

BUB1 and gastric adenocarcinoma

Gastric adenocarcinoma is connected with poor prognosis because tumors often metastasize at the time of diagnosis and prognostic markers are urgently needed to tailor treatment. David Stahl et al. examined the immunohistochemical expression of the mitotic spindle checkpoint protein BUB1 and Ki-67 protein expression in 218 patients with primary gastric adenocarcinoma. Low-frequency tumors with BUB1 expression are associated with larger tumor size (pT), higher rates of lymph node metastasis (pN), distant metastasis (pM), and higher UICC stages. In addition, BUB1 expression was negatively correlated with residual tumor stage. Abundant BUB1 protein expression is associated with frequent Ki-67 protein expression, and low BUB1 expression is associated with shorter survival. Univariate and multivariate analyses confirmed that BUB1 is an independent prognostic marker for gastric cancer.

BUB1 and HCC

Recently, researchers have detected low expression of miR-490-5p in hepatocellular carcinoma (HCC) tissues and cells, while BUB1 is overexpressed compared to controls. Up-regulation of miR-4905p inhibits the expression of BUB1. Overexpression of miR-490-5p or low expression of BUB1 inhibits proliferation, migration, invasion, and apoptosis of HCC cells. Taken together, MiR-490-5p can inhibit the proliferation, invasion and migration of HCC cells, inhibit cell viability and increase apoptosis by inhibiting the regulation of TGFβ/Smad signaling pathway by BUB1.

In conclusion, BUB1 is involved in cell proliferation and plays an important role in the pathogenesis of various cancers. Consequently, further understanding of the role of BUB1 may help to develop new disease diagnosis or cancer treatment strategies.

References:

Xu B, et al. MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells. Pharmacology, 2017, 100(5):269-282
JeongYoon Han, et al. Bub1 is required for maintaining cancer stem cells in breast cancer cell lines. Scientific Reports, 2015, 5: 15993
Adeel Asghar, et al. Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation. Nature Communications, 2015, 6: 8364
David Stahl, et al. Low BUB1 expression is an adverse prognostic marker in gastric adenocarcinoma. Oncotarget, 2017, 8(44):76329-76339

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