Atg4d

BACKGROUND: The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. METHODS: We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease...

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Despite the great advances in autophagy research in the last years, the specific functions of the four mammalian Atg4 proteases (ATG4A-D) remain unclear. In yeast, Atg4 mediates both Atg8 proteolytic activation, and its delipidation. However, it is not clear how these two roles are distributed along the members of the ATG4 family of proteases. We show that these two functions are preferentially carried out by distinct ATG4 proteases, being ATG4D the main delipidating enzyme. In mammalian cells, ATG4D loss results in accumulation of membrane-bound forms of mATG8s, increased cellular autophagosome number and reduced autophagosome average size...

Background: Autophagy is an evolutionally highly conserved process, accompanied by the dynamic changes of various molecules, which is necessary for the orderly degradation and recycling of cellular components. The aim of the study was to identify the role of autophagy-related ( ATG ) genes in the occurrence and development of gastric cancer (GC). Methods: Data from Oncomine dataset was used for the differential expression analysis between cancer and normal tissues...

Autophagy is regulated by a variety of autophagy related genes (ATG), among them, ATG4 is a highly specific protease that is critical to autophagy. The purpose of this study was to investigate the role of the ATG4 response to Palmitic acid (PA) and their relationships with Endoplasmic reticulum (ER) stress in grass carp. In the present study, four ATG4 paralogs from grass carp were identified and analyzed. The open reading frames of ATG4A, ATG4B, ATG4C, and ATG4D were 1212, 1194, 1429, and 1482 bp long, encoding 403, 394, 475, and 493 amino acids, respectively...

Atg4, a pivotal macroautophagy/autophagy-related cysteine protein family, which regulate autophagy through either cleaving Atg8 homologs for its further lipidation or delipidating Atg8 homologs from the autophagosome. There are four homologs, Atg4A, Atg4B, Atg4C, and Atg4D. Among them, an increasing amount of evidence indicates that Atg4B possessed superior catalytic efficiency toward the Atg8 substrate, as well as regulates autophagy process and plays a key role in the development of several human cancers...

Lagotto Romagnolo breed dogs develop a progressive neurological disease with intracellular vacuolar storage when homozygous for a variant in the autophagy-related gene 4D ( ATG4D ). A lysosomal enzyme deficiency has not been proven in this disease, despite its overlapping morphology with lysosomal storage diseases. Instead, basal autophagy was altered in fibroblasts from affected dogs. The aim of this study was to clarify the origin of the limiting membrane of the accumulating vacuoles and determine whether altered basal autophagy affects the extracellular release of vesicles in cells from diseased dogs...

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT...

F-box proteins, as substrates for S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes, mediate the degradation of a large number of regulatory proteins involved in cancer processes. In this study, we found that F-box only protein 2 (FBXO2) was up-regulated in 21 endometrial carcinoma (EC) samples compared with five normal endometrium samples based on our Fudan cohort RNA-sequencing. The increased FBXO2 expression was associated with tumor stage, tumor grade, and histologic tumor type, and poor prognosis based on The Cancer Genome Atlas (TCGA) database...

Prolonged parenchymal cell death leads to activation of fibrogenic cells, extracellular matrix accumulation, and eventually liver fibrosis. Increasing evidence shows that exosomes (Exos) secreted by adipose-derived mesenchymal stem cells (ADSCs) can be used to deliver circular RNAs (circRNAs) to treat liver fibrosis. To explore the uses of circRNA, circRNA expression profiles of hepatic tissue from normal and CCl4 -induced mice were analyzed using high-throughput circRNA microarrays. The result showed that mmu_circ_0000623 expression was downregulated in CCl4 -induced mice...

Background: The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer. Methods: GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes...

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide. Autophagy-related genes (ARGs) may play an essential role in multiple biological processes of prostate cancer. However, ARGs expression signature has rarely been used to investigate the association between autophagy and prognosis in PCa. This study aimed to identify and assess prognostic ARGs signature to predict overall survival (OS) and disease-free survival (DFS) in PCa patients. METHODS: First, a total of 234 autophagy-related genes were obtained from The Human Autophagy Database...

OBJECTIVE: To assess the effect of ulipristal acetate (UPA) on the autophagic process of uterine leiomyoma cells. DESIGN: In vitro study in primary cultures of leiomyoma and myometrial cells isolated from biopsy specimen, and gene expression evaluation in biopsy material. SETTING: Cellular pathology laboratory. PATIENT(S): Premenopausal women (without hormonal treatment) undergoing myomectomy or hysterectomy for symptomatic leiomyomas...

Autophagy is involved in cellular homeostasis and maintenance and may play a role in cardiometabolic health. We aimed to elucidate the role of autophagy in cardiometabolic traits by investigating genetic variants and DNA methylation in autophagy-related genes in relation to cardiovascular diseases and related traits. To address this research question, we implemented a multidirectional approach using several molecular epidemiology tools, including genetic association analysis with genome wide association studies data and exome sequencing data and differential DNA methylation analysis...

BACKGROUND: Due to the poor prognosis and high mortality (over 90%), Pancreas ductal adenocarcinoma (PDAC) is listed as the 7th leading cause of cancer-related death in the world, while gemcitabine sensitivity is key important in PDAC therapy. SNHG14 is thought to be an oncogene in cancer progression. However, the possible role of SNHG14 underlying the progress of the PDAC cell, specifically in gemcitabine resistance remains to be determined. METHODS: We analyzed the PDAC-related data collected from TCGA...

Macroautophagy/autophagy is a cellular degradation pathway that delivers cytoplasmic material to lysosomes via double-membrane organelles called autophagosomes. Lipidation of ubiquitin-like LC3/GABARAP proteins on the autophagosome membrane is important for autophagy. The cysteine protease ATG4 executes 2 LC3/GABARAP processing events: priming of newly synthesized pro-LC3/GABARAP to enable subsequent lipidation, and delipidation/deconjugation of lipidated LC3/GABARAP (the exact purpose of which is unclear in mammals)...

Despite great progress in research on the subject, the involvement of autophagy in colorectal cancer (CRC) pathogenesis (initiation, progression, metastasis) remains obscure and controversial. Autophagy is a catabolic process, fundamental to cell viability and connected with degradation/recycling of proteins and organelles. In this study, we aimed at investigating the relative expression level of mRNA via Real-Time PCR of 16 chosen genes belonging to Atg8 mammalian orthologs and their conjugation system, comprising GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, MAP1LC3C, ATG3, ATG7, ATG10, ATG4A, ATG4B, ATG4C, ATG4D, and three genes encoding proteins building the multimeric ATG16L1 complex, namely ATG5, ATG12, and ATG16L1, in 73 colorectal tumors and paired adjacent normal colon mucosa...

Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, CTSB , ATP6V0C , ATG4D , and WIPI1 , could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the Drosophila homolog of WIPI1 , Atg18a , extended the life span in transgenic flies...

Autophagy is an intracellular degradation system that ensures a dynamic recycling of a variety of building blocks required for self-renewal, homeostasis, and cell survival under stress. We used primary acute myeloid leukemia (AML) samples and human AML cell lines to investigate the regulatory mechanisms of autophagy and its role in AML differentiation. We found a significantly lower expression of key autophagy- (ATG-) related genes in primary AML as compared to healthy granulocytes, an increased autophagic activity during all- trans retinoic acid- (ATRA-) induced neutrophil differentiation, and an impaired AML differentiation upon inhibition of ATG3, ATG4D, and ATG5...