Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9/3, Vienna 1030, Austria.
Biochem Soc Trans. 2010 Feb;38(Pt 1):301-6. doi: 10.1042/BST0380301.
Nuclear intermediate filaments formed by A- and B-type lamins are central components of the nucleoskeleton and are required for the architecture and integrity of the nucleus. There is growing evidence that lamins are also involved in regulatory pathways controlling cell proliferation and differentiation. Lamins affect the activity of several transcription factors, such as retinoblastoma protein and c-Fos, and signalling pathways, such as the ERK1/2 (extracellular-signal-regulated kinase 1/2) and Notch pathways, which are key regulators of cell-cycle progression and differentiation. During mitosis, lamins are dynamically reorganized and play active roles in spindle matrix formation and in post-mitotic nuclear reassembly. Several of the cell-cycle-regulating functions of lamins may be impaired in the diseases linked to mutations in lamins and lamin-associated proteins, including striated muscle diseases, lipodystrophies and premature aging syndromes, and contribute to the tissue-specific disease pathologies.
核纤层蛋白 A 和 B 型形成的核中间丝是核骨架的核心成分，对于核的结构和完整性是必需的。越来越多的证据表明，核纤层蛋白也参与了控制细胞增殖和分化的调节途径。核纤层蛋白影响几种转录因子的活性，如视网膜母细胞瘤蛋白和 c-Fos，以及信号通路，如 ERK1/2（细胞外信号调节激酶 1/2）和 Notch 通路，这些都是细胞周期进程和分化的关键调节因子。在有丝分裂过程中，核纤层蛋白被动态重组，并在纺锤体基质形成和有丝分裂后核重装配中发挥积极作用。核纤层蛋白的几种细胞周期调节功能可能在与核纤层蛋白和核纤层相关蛋白突变相关的疾病中受到损害，包括横纹肌疾病、脂肪营养不良和早衰综合征，并导致组织特异性疾病病理学。
