CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition. CUEDC2 is also known to interact with IkB kinase α (IKKα) and IKKβ and has an inhibitory role in the activation of transcription factor nuclear factor-κB. Moreover, CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptor-α and progesterone receptor, thereby impairing the responsiveness of breast cancer to endocrine therapies. In this review, current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized.
Anaphase-Promoting Complex-Cyclosome ; Breast Neoplasms ; pathology ; Carrier Proteins ; metabolism ; Cell Cycle Proteins ; metabolism ; Cell Transformation, Neoplastic ; pathology ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; I-kappa B Kinase ; metabolism ; Inflammation ; pathology ; M Phase Cell Cycle Checkpoints ; Membrane Proteins ; metabolism ; Mitosis ; NF-kappa B p50 Subunit ; metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases ; metabolism ; Signal Transduction ; Ubiquitin-Protein Ligase Complexes ; metabolism ; Ubiquitination

Objective To investigate the effect and mechanism of bromodomain-containing protein 2(BRD2)on regulation of antitumor immunity,and to explore a novel target for immunotherapy.Methods The REMBRANDT glioma database and GlioVis and TIMER websites were used to compare the expression levels of BRD2 in tumor tissues and normal ones.The correlations between BRD2 expression levels and the prognosis of patients with glioblastoma multiforme(GBM)and those between BRD2 expression levels and immune cell infiltration in GBM were studied.The interference plasmid targeting the BRD2 gene was constructed.The lentivirus was packaged and used to infect murine glioma cells GL261.The positive cells were screened with blasticidin for 6 days,and the expression level of BRD2 protein was detected by Western blot.The CellTiter-Glo kit was used to detect the cell viability of GL261 cells after BRD2 knockdown,which were transplanted into the subcutaneous tissue of C57BL/6J mice to form subcutaneous tumors.The tumor volume was measured periodically.Twenty-eight days after tumor inoculation,the tumors were removed and tumor cells isolated.The infiltration of CD8+T cells within the subcutaneous tumor tissue was analyzed using flow cytometry and immunohistochemistry.Results BRD2 was highly expressed in a variety of tumor tissues.The prognosis of glioma patients with high BRD2 expressions was poor,and the BRD2 expression level was negatively correlated with CD8+T cell infiltration in the tumor.The growth rate of subcutaneously transplanted GL261 tumor cells after BRD2 knockdown was decelerated,and the infiltration level of CD8+T cells in subcutaneous tumor tissue was increased.Conclusion BRD2 over-expression inhibits the infiltration of CD8+T cells in GBM tumors and promotes the growth of tumors.