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PXD002844

PXD002844 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleQuantitative analysis to the subcellular proteome in response to cathepsin D knockdown in HeLa cells
DescriptionCathepsin D is reportedly to be closely associated with tumor development, migration and invasion, but its pathological mechanism is not fully elucidated. We aimed to evaluate phenotypic changes and molecular events in response to cathepsin D knockdown. Lowering endogenous cathepsin D abundance (CR) induced senescence in HeLa cells, leading to reduced rate of cell proliferation and impaired tumorigenesis in a mouse model. Quantitative proteomics revealed that compared with control cells (EV), the abundances of several typical lysosomal proteases were decreased in the lysosomal fraction in CR cells. We further showed that cathepsin D knockdown caused increased permeability of lysosomal membrane and ROS accumulation in CR cells, and the scavenging of ROS by antioxidant was able to rescue cell senescence. Despite the increased ROS, the proteomic data suggested a global reduction of redox-related proteins in CR cells. Subsequent analysis indicated that the transcriptional activity of nuclear factor erythroid-related factor 2 (Nrf2), which regulates the expression of groups of antioxidant enzymes, was down-regulated by cathepsin D knockdown. Importantly, Nrf2 over-expression significantly reduced cell senescence. Although transient oxidative stress promoted the accumulation of Nrf2 in the nucleus, we showed that the Nrf2 protein exited nucleus if oxidative stress persisted. In addition, when cathepsin D was transiently knocked down, the cathepsin-related events followed a sequential order, including lysosomal leakage during the early stage, followed by oxidative stress augmentation, and ultimately Nrf2 down-regulation and senescence. Our results suggest the roles of cathepsin D in cancer cells in maintaining lysosomal integrity, redox balance and Nrf2 activity, thus promoting tumorigenesis.
HostingRepositoryPRIDE
AnnounceDate2015-12-17
AnnouncementXMLSubmission_2015-12-17_03:56:17.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSiyuan Su
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-09-02 23:45:48ID requested
12015-12-17 03:56:19announced
Publication List
Su S, Zhu X, Lin L, Chen X, Wang Y, Zi J, Dong Y, Xie Y, Zhu Y, Zhang J, Zhu J, Xu D, Xu N, Lou X, Liu S, Lowering Endogenous Cathepsin D Abundance Results in Reactive Oxygen Species Accumulation and Cell Senescence. Mol Cell Proteomics, 16(7):1217-1232(2017) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: SILAC, cytosol, lysosome, nucleus, subcellular fractionation
Contact List
Siqi Liu
contact affiliationBeijing Institute of Genomics, Chinese Academy of Sciences
contact emailsiqiliu@big.ac.cn
lab head
Siyuan Su
contact affiliationBeijing Institute of Genomics, CAS
contact emailsusy@big.ac.cn
dataset submitter
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Dataset FTP location
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