The nuclear envelope is composed by an outer nuclear membrane and an inner nuclear membrane, which is underlain by the nuclear lamina that provides the nucleus with mechanical strength for maintaining structure and regulates chromatin organization for modulating gene expression and silencing. A layer of heterochromatin is beneath the nuclear lamina, attached by inner nuclear membrane integral proteins such as Lamin B receptor (LBR). LBR is a chimeric protein, having also a sterol reductase activity with which it contributes to cholesterol synthesis. Lukasova et al. showed that when DNA is damaged by ɣ-radiation in cancer cells, LBR is lost causing chromatin structure changes and promoting cellular senescence. Cellular senescence is characterized by terminal cell cycle arrest and the expression and secretion of various growth factors, cytokines, metalloproteinases, etc., collectively known as senescence-associated secretory phenotype (SASP) that cause chronic inflammation and tumor progression when they persist in the tissue. Therefore, it is fundamental to understand the molecular basis for senescence establishment, maintenance and the regulation of SASP. The work of Lukasova et al. contributed to our understanding of cellular senescence establishment and provided the basis that lead to the further discovery that chromatin changes caused by LBR reduction induce an up-regulated expression of SASP factors. LBR dysfunction has relevance in several diseases and possibly in physiological aging. The potential bifunctional role of LBR on cellular senescence establishment, namely its role in chromatin structure together with its enzymatic activity contributing to cholesterol synthesis, provide a new target to develop potential anti-aging therapies.

中文翻译：

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核纤层蛋白 B 受体：对染色质结构、细胞衰老和可能的衰老的作用。


核膜由外核膜和内核膜组成，核膜下方是核纤层，为细胞核提供维持结构的机械强度，并调节染色质组织以调节基因表达和沉默。核纤层下方有一层异染色质，由内核膜整合蛋白（例如核纤层蛋白 B 受体 (LBR)）附着。 LBR 是一种嵌合蛋白，还具有甾醇还原酶活性，有助于胆固醇合成。卢卡索娃等人。研究表明，当癌细胞中的 DNA 受到 ɣ 辐射损伤时，LBR 会丢失，导致染色质结构发生变化并促进细胞衰老。细胞衰老的特点是细胞周期末期停滞以及各种生长因子、细胞因子、金属蛋白酶等的表达和分泌，统称为衰老相关分泌表型（SASP），当它们持续存在于组织中时会引起慢性炎症和肿瘤进展。因此，了解SASP衰老建立、维持和调节的分子基础至关重要。卢卡索娃等人的工作。有助于我们对细胞衰老建立的理解，并为进一步发现LBR减少引起的染色质变化诱导SASP因子表达上调提供了基础。 LBR 功能障碍与多种疾病相关，并可能与生理衰老相关。 LBR 在细胞衰老建立中的潜在双功能作用，即其在染色质结构中的作用及其有助于胆固醇合成的酶活性，为开发潜在的抗衰老疗法提供了新的靶点。