Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015.
Mol Biol Cell. 2023 May 1;34(5):rs2. doi: 10.1091/mbc.E22-12-0557. Epub 2023 Mar 22.
Cohesins are ATPase complexes that play central roles in cellular processes such as chromosome division, DNA repair, and gene expression. Cohesinopathies arise from mutations in cohesin proteins or cohesin complex regulators and encompass a family of related developmental disorders that present with a range of severe birth defects, affect many different physiological systems, and often lead to embryonic fatality. Treatments for cohesinopathies are limited, in large part due to the lack of understanding of cohesin biology. Thus, characterizing the signaling networks that lie upstream and downstream of cohesin-dependent pathways remains clinically relevant. Here, we highlight alterations in cohesins and cohesin regulators that result in cohesinopathies, with a focus on cardiac defects. In addition, we suggest a novel and more unifying view regarding the mechanisms through which cohesinopathy-based heart defects may arise.
黏连蛋白是一种 ATP 酶复合物,在细胞分裂、DNA 修复和基因表达等细胞过程中发挥核心作用。黏连蛋白病是由黏连蛋白蛋白或黏连蛋白复合物调节剂的突变引起的,包括一系列相关的发育障碍疾病,其表现为一系列严重的出生缺陷,影响许多不同的生理系统,并且经常导致胚胎死亡。黏连蛋白病的治疗方法有限,在很大程度上是由于对黏连蛋白生物学缺乏了解。因此,描述黏连蛋白依赖性途径上下游的信号网络仍然具有临床意义。在这里,我们重点介绍了导致黏连蛋白病的黏连蛋白和黏连蛋白调节剂的改变,以及心脏缺陷。此外,我们提出了一种关于基于黏连蛋白病的心脏缺陷可能发生的机制的新颖且更统一的观点。