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CDCA5与肿瘤
编辑人员丨5天前
姐妹染色单体凝聚发生于DNA复制时期,由黏合素调节,并且依赖于细胞分裂周期相关蛋白5(CDCA5)及黏合素的乙酰化。WAPL可以促进黏合素与DNA解离,CDCA5可以拮抗WAPL的作用,通过稳定黏合素与DNA的结合从而稳定姐妹染色单体凝聚。CDCA5 mRNA在多种肿瘤细胞株中具有较高的转录水平,提示CDCA5可能与肿瘤细胞较高的恶性增殖活性有关,并且已经在肝癌、肺癌等多种肿瘤中得到证实,CDCA5可能是肿瘤治疗的潜在靶向分子。
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编辑人员丨5天前
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Regulation of sister chromatid cohesion by nuclear PD-L1
编辑人员丨2023/8/5
Programmed death ligand-1 (PD-L1 or B7-H1) is well known for its role in immune checkpoint regulation,but its function inside the tumor cells has rarely been explored.Here we report that nuclear PD-L1 is important for cancer cell sister chromatid cohesion.We found that depletion of PD-L1 suppresses cancer cell proliferation,colony formation in vitro,and tumor growth in vivo in immunedeficient NSG mice independent of its role in immune checkpoint.Specifically,PD-L1 functions as a subunit of the cohesin complex,and its deficiency leads to formation of multinucleated cells and causes a defect in sister chromatid cohesion.Mechanistically,PD-L1 compensates for the loss of Sororin,whose expression is suppressed in cancer cells overexpressing PD-L1.PD-L1 competes with Wing Apart-Like (WAPL) for binding to PDS5B,and secures proper sister chromatid cohesion and segregation.Our findings suggest an important role for nuclear PD-L1 in cancer cells independent of its function in immune checkpoint.
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编辑人员丨2023/8/5