LMNA P02545

前核纤层蛋白-A/C [裂解为：核纤层蛋白-A/C (70 kDa核纤层蛋白) (肾癌抗原 NY-REN-32)]

功能描述

[Lamin-A/C]: Lamins是中间纤维蛋白，组装成纤维网状结构，构成核纤层的主要成分，核纤层是位于内核膜核质侧的纤维层 (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547)。Lamins为核膜提供支架，连接核膜和染色质，从而在核组装、染色质组织、核膜和端粒动力学中发挥重要作用 (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547)。Lamin A和C还通过赋予核机械特性来调节基质硬度 (PubMed:23990565, PubMed:25127216)。核纤层的结构完整性受到细胞周期的严格控制，正如前期和末期分别出现的核膜解体和形成所示 (PubMed:2188730, PubMed:2344612)。Lamin A和C在哺乳动物的核纤层中以等量存在 (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606)。也参与DNA修复：被DNA修复蛋白XRCC4和IFFO1招募至DNA双链断裂（DSBs）处，通过固定断裂的DNA末端来防止染色体易位 (PubMed:31548606)。为周围神经系统和骨骼肌的正常发育以及肌肉卫星细胞增殖所必需 (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096)。为成骨细胞生成和骨形成所必需 (PubMed:12075506, PubMed:15317753, PubMed:18611980)。还能防止脂肪浸润肌肉和骨髓，有助于维持骨骼肌和骨的体积与强度 (PubMed:10587585)。为心脏稳态所必需 (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920)。 {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C可加速平滑肌细胞衰老 (PubMed:20458013)。它作用于破坏血管平滑肌细胞（VSMCs）的有丝分裂并诱导DNA损伤，导致有丝分裂失败、基因组不稳定和过早衰老 (PubMed:20458013)。 {ECO:0000269|PubMed:20458013}.

组织特异性

In the arteries, prelamin-A/C accumulation is not observed in young healthy vessels but is prevalent in medial vascular smooth muscle cells (VSMCs) from aged individuals and in atherosclerotic lesions, where it often colocalizes with senescent and degenerate VSMCs. Prelamin-A/C expression increases with age and disease. In normal aging, the accumulation of prelamin-A/C is caused in part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative stress.

亚细胞定位

Nucleus lamina