@article{c64ce69a6105485ebd5f0c09279bc6ea,
title = "Autophagy mediates degradation of nuclear lamina",
abstract = "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.",
author = "Zhixun Dou and Caiyue Xu and Greg Donahue and Takeshi Shimi and Pan, {Ji An} and Jiajun Zhu and Andrejs Ivanov and Capell, {Brian C.} and Drake, {Adam M.} and Shah, {Parisha P.} and Catanzaro, {Joseph M.} and Ricketts, {M. Daniel} and Trond Lamark and Adam, {Stephen A.} and Ronen Marmorstein and Zong, {Wei Xing} and Terje Johansen and Goldman, {Robert D.} and Adams, {Peter D.} and Berger, {Shelley L.}",
note = "Funding Information: Acknowledgements We thank members of the Berger, Adams, and Goldman laboratories for technical assistance and discussions. We acknowledge A. L. Stout for help with confocal microscopy, and the electron microscopy resource laboratory for assistance on TEM. We thank Z. Yue for sharing the GFP antibody and reading the manuscript, and M. Narita and R. Salama for help with LADs definition. Z.D. is supported by a fellow award from the Leukemia & Lymphoma Society. B.C.C. is supported by career development awards from the Dermatology Foundation, Melanoma Research Foundation, and American Skin Association. S.L.B., P.D.A. and R.M. are supported by NIA P01 grant (P01AG031862). S.L.B. is also supported by NIH R01 CA078831. R.D.G. is supported by R01 GM106023 and the Progeria Research Foundation. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = nov,
day = "5",
doi = "10.1038/nature15548",
language = "English (US)",
volume = "527",
pages = "105--109",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7576",
}