Autophagy mediates degradation of nuclear lamina

Zhixun Dou, Caiyue Xu, Greg Donahue, Takeshi Shimi, Ji An Pan, Jiajun Zhu, Andrejs Ivanov, Brian C. Capell, Adam M. Drake, Parisha P. Shah, Joseph M. Catanzaro, M. Daniel Ricketts, Trond Lamark, Stephen A. Adam, Ronen Marmorstein, Wei Xing Zong, Terje Johansen, Robert D. Goldman, Peter D. Adams, Shelley L. Berger*

*Corresponding author for this work

Research output: Contribution to journalArticle

234 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)105-109
Number of pages5
JournalNature
Volume527
Issue number7576
DOIs
StatePublished - Nov 5 2015

ASJC Scopus subject areas

  • General

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    Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J. A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., Catanzaro, J. M., Ricketts, M. D., Lamark, T., Adam, S. A., Marmorstein, R., Zong, W. X., Johansen, T., Goldman, R. D., Adams, P. D., & Berger, S. L. (2015). Autophagy mediates degradation of nuclear lamina. Nature, 527(7576), 105-109. https://doi.org/10.1038/nature15548