ABSTRACT Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins’ function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins’ function in the nuclear interior.

中文翻译：

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核纤层蛋白磷酸化：在纤层蛋白病的基因调控和发病机制中的新兴作用

摘要 数十年的研究已经确定，核纤层蛋白聚合物形成核纤层，这是一种支持核膜结构并将异染色质连接到核外围的蛋白质网络。关于核内部未聚合的核纤层蛋白知之甚少，现在已知其中一些会经历特定的磷酸化。最近发现磷酸化的核纤层蛋白结合基因增强子区域提供了一个新的假设，即核纤层蛋白磷酸化可能影响核内部的转录调控。在这篇综述中，我们讨论了磷酸化核纤层蛋白的调节、定位和功能。我们总结了在各种生物环境中磷酸化核纤层蛋白的激酶。我们的讨论延伸到椎板病，一种由 lamin 基因突变引起的退行性疾病，如心肌病和早衰症。我们将基于核纤层蛋白在核层的功能的流行假设与基于磷酸化核纤层蛋白在核内部的功能的新兴假设进行比较。