Ctsd

Case study 1: Eleonora Secomandi, 2022

Neuroblastoma is a malignant extracranial solid tumor arising from the sympathoadrenal lineage of the neural crest and is often associated with N-MYC amplification. Cathepsin D has been associated with chemoresistance in N-MYC-overexpressing neuroblastomas. Increased EGFR expression also has been associated with the aggressive behavior of neuroblastomas. This work aimed to understand the mechanisms linking EGFR stimulation and cathepsin D expression with neuroblastoma progression and prognosis.

Low CTSD expression was associated with poor clinical outcome. CTSD expression was negatively correlated with CCNB2, CCNA2, CDK1 and CDK6 genes involved in cell cycle division. Cathepsin D overexpression decreased the proliferative potential of neuroblastoma cells through downregulation of the pro-oncogenic MAPK signaling pathway. EGFR stimulation downregulated cathepsin D expression, thus favoring cell cycle division.

Fig1. Western blot of cathepsin D in SH-SH5Y Sham, 486 (KD-CD) and Over CD clones.

Fig2. Western blot of phospho-ERK 1/2 and total protein in Sham cell homogenates at different time points (24, 48, and 72 h) in the presence/absence of EGF.

Case study 2: Yuan Li, 2017

This study aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2'-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way.

AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs.
This study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway.

Fig3. CTSD was successfully transfected into cells. Green cells were labelled with green fluorescent protein, which indicated the transfection was successful.

Fig4. The protein expression of LC3-II, LC3-I, p62, and CTSD were analyzed using western blotting after CTSD was transfected into cells.

Ctsd involved in several pathways and played different roles in them. We selected most pathways Ctsd participated on our site, such as Adaptive Immune System, Ceramide signaling pathway, Collagen degradation, which may be useful for your reference. Also, other proteins which involved in the same pathway with Ctsd were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Ctsd has several biochemical functions, for example, aspartic-type endopeptidase activity, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Ctsd itself. We selected most functions Ctsd had, and list some proteins which have the same functions with Ctsd. You can find most of the proteins on our site.

Ctsd has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Ctsd here. Most of them are supplied by our site. Hope this information will be useful for your research of Ctsd.

env; APP; hly; HBA1; MAPK1; purT; q7cjw2_yerpe; leuD; RASSF10; ere_dna; RASSF9; cona_canen; H2AFX; VCAM1; ATP6V1A; RASSF7

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