As one of the spindle checkpoints, the BUBl protein plays an important role in maintaining chromosome separation and reducing aneuploidy during mitosis. In addition to ensuring correct chromosome segregation, BUB1 is essential for mediating cell death when chromosomes are not segregated. BUB1, as a platform protein for the spindle checkpoint, is the basis for positioning other components of the spindle checkpoint on the spindle. BUB1 plays an important role in the assembly of the spindle assembly checkpoint (SAC) and the alignment of chromosomes and equatorial plates during mitosis. In addition, the BUB1 gene plays an important regulatory role in biological processes such as cell cycle and apoptosis. Studies have shown that BUB1 can regulate other important spindle checkpoint proteins through direct action or in the form of complexes, thereby affecting the progress of the cell cycle. When SAC is activated, BUB1 first phosphorylates BUB3, forms a BUB1-BUB3 complex with it, and then phosphorylates CDC20, a co-activator of APC/C. Phosphorylated CDC20 eventually leads to a decrease in APC/C activity, thereby inhibiting the cells from transitioning from middle to late mitosis. The abnormality of the BUB1 gene may lead to a phenotypic change in cancer susceptibility. BUB1 gene mutation inactivation is very rare in human cancers, and only low frequency mutations exist in certain human tumors with chromosomal instability and aneuploidy. BUB1 is abnormally expressed in a variety of human cancers, including colorectal, gastric, esophageal, and endometrial cancers.

Figure 1. Protein structure of BUB1.

BUB1 gene in endometrial cancer

BUB1 gene may play an important role in the occurrence, development, prognosis and treatment of endometrial cancer. Bioinformatics analysis of endometrial cancer RNA sequencing data in the TCGA database reveals that BUB1 may be one of several key pivot genes in endometrial cancer. The expression of BUB1 gene is closely related to the pathological type, degree of differentiation, and tumor stage of endometrial cancer. There is a difference in expression between endometrioid cancer and non-endometrioid cancer, and the expression of BUB1 in non-endometrioid cancer high. The positive expression rate of BUB1 protein in normal endometrium, complex hyperplasia endometrium and endometrial cancer tissue gradually decreases. The lower the degree of differentiation of endometrial cancer or the later the clinical stage, the lower the positive rate of BUB1 protein, but the positive rate was not related to the presence or absence of lymph node metastasis. In addition, the expression of BUB1, mutant p53 (Mtp53) protein, and MAD2 protein in endometrial cancer tissues is negatively correlated, which is considered to be related to the occurrence and development of endometrial cancer. The combined detection of BUB1 and Mtp53 proteins, and BUB1 and MAD2 Protein may have some prognostic significance.

Functions

The protein kinase Bub1 has multiple functions and unique functions in the cell cycle, mainly in SAC and metaphase chromosome alignment. The protein interaction networks identified so far are also very complex. In eukaryotic cells, SAC acts as a central monitoring mechanism to ensure that chromosomes are passed on to the next generation in a reliable manner. Several components may monitor the correct bipolar connection of microtubules to kinema by detecting tension. As long as a single animal or plant lacks bipolar microtubule attachment, SAC will stop the mid-to-late transition, which means a highly sensitive signal pathway is needed. Bub1 is said to be a major regulator of SAC formation and signaling. After SAC activation, Bub1 directly phosphorylates the APC/C coactivator Cdc20. This phosphorylation may form a complex with Bub3, which is pre-phosphorylated by Bub1 itself.

Conclusions

In summary, BUB1 is an important spindle checkpoint protein, which has the role of promoting tumorigenesis through chromosomal instability and aneuploidy passage. Plays an important role. Explore the role of BUB1 in gynecological tumors and related mechanisms.

Reference:

1. Bolanos-Garcia VM; et al. The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores. Structure. 2009, 17 (1): 105–16.