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Series GSE63440 Query DataSets for GSE63440
Status Public on Oct 08, 2015
Title Autophagy mediates degradation of nuclear lamina
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Autophagy is a catabolic membrane trafficking process involved in degradation of cellular constituents through lysosomes, which maintains cell and tissue homeostasis. While much attention has been focused on autophagic turnover of cytoplasmic materials, little is known regarding the role of autophagy in degrading nuclear components. Here we report that autophagy machinery mediates degradation of nuclear lamina in mammalian cells, a process we term laminophagy. The autophagy protein LC3 is present in the nucleus and directly interacts with the nuclear lamina protein Lamin B1, and associates with lamin-associated domains (LADs) on chromatin. This interaction does not downregulate Lamin B1 during starvation, but mediates nuclear lamina degradation upon tumorigenic insults, such as by oncogenic Ras. Laminophagy is achieved by nucleus-to-cytosol transport that delivers Lamin B1 to lysosome for degradation. Inhibiting autophagy or LC3-Lamin B1 interaction prevents oncogenic Ras-induced Lamin B1 loss and delays oncogene-induced cell cycle arrest. Our study unveils a role of autophagy in degrading nuclear materials, and suggests laminophagy as a guarding mechanism protecting cells from tumorigenesis.
Overall design Study includes two replicates each of lamin B1, LC3, and input to control for sonication efficiency. Only one condition is included.
Contributor(s) Dou Z, Xu C, Donahue G, Shimi T, Pan J, Zhu J, Ivanov A, Capell BC, Drake AM, Shah PP, Catanzaro JM, Ricketts MD, Lamark T, Adam SA, Marmorstein R, Zong W, Johansen T, Goldman RD, Adams PD, Berger SL
Citation(s) 26524528
Submission date Nov 18, 2014
Last update date May 15, 2019
Contact name Gregory Donahue
Organization name The University of Pennsylvania
Department Cell & Developmental Biology
Lab Zaret Lab
Street address 3400 Civic Center Blvd, Bldg 421
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (6)
GSM1827553 Lamin B1, Replicate 1
GSM1827554 Lamin B1, Replicate 2
GSM1827555 LC3, Replicate 1
BioProject PRJNA267739
SRA SRP050018

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Supplementary file Size Download File type/resource
GSE63440_RAW.tar 3.1 Gb (http)(custom) TAR (of BED, BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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