Selective Autophagy Regulates Cell Cycle in Cancer Therapy

Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment. Indeed, survival of many cancers exclusively relies on these proteins, and several specific inhibitors are in clinical use. Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery. However, these studies have often led to divergent rather than unifying explanations due to complexity of the autophagy signaling network, the inconsistent functions between general autophagy and selective autophagy, and the different characteristics of autophagic substrates. In this review, we highlight current data illustrating the contradictory and important role of cell cycle proteins in regulating autophagy. We also focus on how selective autophagy acts as a central mechanism to maintain orderly DNA repair and genome integrity by degrading specific cell cycle proteins, regulating cell division, and promoting DNA damage repair. We further discuss the ways in which selective autophagy may impact the cell cycle regulators, since failure to appropriately remove these can interfere with cell death-related processes, including senescence and autophagy-related cell death. Imbalanced cell proliferation is ...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research

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In conclusion, it remains unclear if brain-specific regional and temporal changes occur in the expression of the different APP variants during AD progression. Since APP is also found in blood cells, assessing the changes in APP mRNA expression in peripheral blood cells from AD patients has been considering an alternative. However, again the quantification of APP mRNA in peripheral blood cells has generated controversial results. Brain APP protein has been analyzed in only a few studies, probably as it is difficult to interpret the complex pattern of APP variants and fragments. We previously characterized the soluabl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The fasting mimicking diet emerged from efforts to better define the dose-response curve for beneficial effects resulting from a reduced calorie intake. Fasting is beneficial, calorie restriction is beneficial, but where are the dividing lines? How much food can one eat and still obtain near all of the benefits of fasting? As a result of this work, the fasting mimicking diet has undergone clinical testing in cancer patients. Numerous benefits have been demonstrated, and the paper here is an example of the type. In this human trial, fasting mimicking reduced the negative short term impact of chemotherapy on health, and, fur...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
AbstractMicrosatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci len...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Breast and ovarian cancer are among the most frequent causes of cancer-related deaths in women worldwide. Genomic instability is prevalent in these cancer types, and it has been associated with mutations in DNA repair genes, including the BRCA1 and BRCA2 tumor suppressor genes. FEN1 and Homologous Recombination Defects A synthetic...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Commentaries Source Type: research
In this study, we explored the effects of Galloflavin and Ellagic acid, the most common polyphenols in berries, on SIRT6. SIRT6 deacetylation was investigated using HPLC and immunoblotting assays. The expression levels of SIRT6, glycolytic proteins and cellular metabolism were studied on human colon adenocarcinoma cells (Caco2). Molecular docking studies were carried out to study possible interactions of the compounds with sirtuins. Ellagic acid increased the deacetylase activity of SIRT6 by up to 50-fold; it showed moderate inhibition of SIRT1-3. Galloflavin and Ellagic acid showed anti-proliferative effects on Caco2. The...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
Abstract Isocitrate dehydrogenase active-site mutations cause a neomorphic enzyme activity that results in the formation of supraphysiological concentrations of D-2-hydroxyglutarate (D-2HG). D-2HG is thought to be an oncometabolite that drives the formation of cancers in a variety of tissue types by altering the epigenetic state of progenitor cells by inhibiting enzymes involved in histone and DNA demethylation. This model has led to the development of pharmacological inhibitors of mutant IDH activity for anti-cancer therapy, which are now being tested in several clinical trials. Emerging evidence in preclinical g...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Abstract Applications of non-thermal plasma (NTP) discharges in medicine, particularly cancer therapy, have increased in recent years. The aim of the present study was to investigate the advantages of the combined application of NTP-irradiated acetated Ringer's solution (PAA) and hyperthermia, a heat treatment at 42 °C, on A549 cancer cell death and elucidate the underlying mechanisms. Cell death was enhanced more by the above combined treatment and was accompanied by increases in intracellular calcium ([Ca2+]i). The activation of transient receptor potential melastatin 2 (TRPM2) may enhance cell death becau...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research
n Zhang DNA replication is the fundamental process for accurate duplication and transfer of genetic information. Its fidelity is under constant stress from endogenous and exogenous factors which can cause perturbations that lead to DNA damage and defective replication. This can compromise genomic stability and integrity. Genomic instability is considered as one of the hallmarks of cancer. In normal cells, various checkpoints could either activate DNA repair or induce cell death/senescence. Cancer cells on the other hand potentiate DNA replicative stress, due to defective DNA damage repair mechanism and unchecked growth...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
We report that electrical stimulation (ES) stimulation of post-stroke aged rats led to an improved functional recovery of spatial long-term memory (T-maze), but not on the rotating pole or the inclined plane, both tests requiring complex sensorimotor skills. Surprisingly, ES had a detrimental effect on the asymmetric sensorimotor deficit. Histologically, there was a robust increase in the number of doublecortin-positive cells in the dentate gyrus and SVZ of the infarcted hemisphere and the presence of a considerable number of neurons expressing tubulin beta III in the infarcted area. Among the genes that were unique...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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