Autophagy mediates degradation of nuclear lamina
By Zhixun Dou, Caiyue Xu, Greg Donahue, Takeshi Shimi, Ji-An Pan, Jiajun Zhu, Andrejs Ivanov, Brian C. Capell, Adam M. Drake, P. Shah and 10 more. Nature, 2015
609 citations recorded by the source corpus.
Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3–lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3–lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.
Subfields: Cell Biology, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/a7a3988fe979a8b9e87e493dec02ee9d4937da19
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Citations in the corpus
- Mechanisms and functions of cellular senescence. (2018, neutral): “Another consequence of the autophagy-mediated degradation of LMNB1 observed in senescence (110) is compromised integrity of the nuclear envelope, which may lead to the observed blebbing of cytoplasmic chromatin fragments (CCFs) (111).”
- Autophagy-Dependent Ferroptosis: Machinery and Regulation (2020, background): “Nucleophagy-associated lamin B1 (LMNB1) degradation is associated with oncogenic RAS activation, but not starvation (Dou et al., 2015).”
- Hallmarks of Cellular Senescence. (2018, positive): “Once in the nucleus, it is submitted for degradation by the lysosomes [156].”
- Cellular Senescence: Defining a Path Forward. (2019, positive): “Downregulation of lamin B1, a major component of the nuclear lamina, is another key feature of senescence (Dou et al., 2015; Freund et al., 2012; Shah et al., 2013; Shimi et al., 2011).”