Abstract:
:We analyzed the cellular and molecular effects of two different histone deacetylase inhibitors (HDACi), MGCD0103 and vorinostat, in combination with GX15-070, a BH3-mimetic, in acute myeloid leukemia (AML) cell lines and primary AML cells, and demonstrated that the combination has a synergistic antileukemia effect. We observed that in addition to apoptosis, autophagy also accounts for the observed nonapoptotic decrease of cell viability. Mechanistically, we established a role for calpain activity and ER-located caspase signaling in the induction of both autophagy and apoptosis following this combination of drugs. These findings reveal that for this specific combination, autophagy plays a positive role in inducing cytotoxicity, and that the involved ER signaling networks, as well as their clinical relevance, should be further studied in both preclinical and clinical trials of leukemia and other malignancies.
journal_name
Autophagyjournal_title
Autophagyauthors
Wei Y,Kadia T,Tong W,Zhang M,Jia Y,Yang H,Hu Y,Viallet J,O'Brien S,Garcia-Manero Gdoi
10.4161/auto.6.7.13117subject
Has Abstractpub_date
2010-10-01 00:00:00pages
976-8issue
7eissn
1554-8627issn
1554-8635pii
13117journal_volume
6pub_type
杂志文章相关文献
Autophagy文献大全abstract::Damaged mitochondria are turned over through a process of selective autophagy termed mitophagy. In mitophagy, unhealthy mitochondria are recognized and ubiquitinated by Parkinson disease-linked proteins PINK1 and PARK2. The subsequent recruitment of ubiquitin-binding autophagy receptors leads in turn to the sequestrat...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1212788
更新日期:2016-10-02 00:00:00
abstract::The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are the two most important components of cellular mechanisms for protein degradation. In the present study we investigated the functional relationship of the two systems and the interactional role of p53 in vitro. Our study showed that the...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.5.8377
更新日期:2009-07-01 00:00:00
abstract::Most autophagy-related (Atg) proteins are assembled at the phagophore assembly site or pre-autophagosomal structure (PAS), which is a potential site for vesicle formation during vegetative or starvation conditions. To understand the initial step of vesicle formation, it is important to know how Atg proteins are recrui...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6375
更新日期:2008-07-01 00:00:00
abstract::DBI/ACBP (diazepam binding protein, acyl-CoA binding protein) participates in the regulation of fatty acid metabolism when it is localized within cells, whereas outside of cells it acts as a diazepam-binding protein. Recent results indicate that many different mammalian cell types release DBI/ACBP upon in vitro or in ...
journal_title:Autophagy
pub_type: 评论,杂志文章
doi:10.1080/15548627.2019.1662585
更新日期:2019-11-01 00:00:00
abstract::Delivery of cellular contents to yeast vacuoles/mammalian lysosomes via autophagy ensures long-term cell survival and extends life span. When cultured yeast cells are grown for a prolonged period of time to enter stationary phase, a nondividing state mimicking quiescence, vacuolar membrane proteins partition into eith...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.36137
更新日期:2014-01-01 00:00:00
abstract::Phagocytosis and macroautophagy/autophagy are 2 processes involved in lysosome-mediated clearance of extracellular and intracellular components, respectively. Recent studies have identified the recruitment of the autophagic protein LC3 during phagocytosis of apoptotic corpses in what is now called LC3-associated phago...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2018.1512452
更新日期:2019-02-01 00:00:00
abstract::The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivatio...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2020.1725381
更新日期:2020-02-16 00:00:00
abstract::Autophagy is a conserved homeostatic process in which cytoplasmic contents are degraded and recycled. Two ubiquitin-like conjugation pathways are required for the generation of autophagosomes, and ATG5 is necessary for both of these processes. Studies of mice deficient in ATG5 reveal a key role for autophagy in T lymp...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.23484
更新日期:2013-04-01 00:00:00
abstract::Based on my reading, and on my own experience, I have come to realize that people learn in different ways, and this can include the use of different media. This is one reason I have worked with various artists to portray the topic of autophagy through paintings, music and dance. Indeed, comments from members of the au...
journal_title:Autophagy
pub_type: 评论,社论
doi:10.1080/15548627.2019.1630225
更新日期:2019-09-01 00:00:00
abstract::Macroautophagy/autophagy occurs at basal levels in all eukaryotic cells and plays an important role in maintaining bio-energetic homeostasis through the control of molecule degradation and organelle turnover. It can be induced by environmental conditions such as starvation, and is deregulated in many diseases includin...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.1080/15548627.2019.1630223
更新日期:2020-01-01 00:00:00
abstract::During reticulocyte maturation, hematopoietic progenitors undergo numerous changes to reach the final functional stage which concludes with the release of reticulocytes and erythrocytes into circulation. During this process some proteins, which are not required in the mature stage, are sequestered in the internal vesi...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.2.2.2350
更新日期:2006-04-01 00:00:00
abstract::Lafora disease (LD) is an inherited and fatal form of neurodegenerative disorder characterized by the presence of an abnormal form of glycogen inclusions, called Lafora bodies, in neurons and other tissues. While Lafora bodies have been thought to underlie the neuropathology in LD, the specific process by which these ...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.8.2.19010
更新日期:2012-02-01 00:00:00
abstract::The endothelium plays a central role in the regulation of vascular wall cellularity and tone by secreting an array of mediators of importance in intercellular communication. Nutrient deprivation of human endothelial cells (EC) evokes unconventional forms of secretion leading to the release of nanovesicles distinct fro...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.19768
更新日期:2012-06-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (B...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1308997
更新日期:2017-06-03 00:00:00
abstract::A shared neuropathological hallmark in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is nuclear clearance and cytoplasmic aggregation of TARDBP/TDP-43 (TAR DNA binding protein). We previously showed that the ability of TARDBP to repress nonconserved cryptic exons was impaired in brains of patie...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2019.1635379
更新日期:2020-04-01 00:00:00
abstract::Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnos...
journal_title:Autophagy
pub_type: 杂志文章,多中心研究
doi:10.4161/auto.28984
更新日期:2014-08-01 00:00:00
abstract::Genetic inactivation of PTEN through either gene deletion or mutation is common in metastatic prostate cancer, leading to activation of the phosphoinositide 3-kinase (PI3K-AKT) pathway, which is associated with poor clinical outcomes. The PI3K-AKT pathway plays a central role in various cellular processes supporting c...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.24921
更新日期:2013-07-01 00:00:00
abstract::ISG15 (ISG15 ubiquitin-like modifier), a ubiquitin-like protein, is one of the major type I IFN (interferon) effector systems. ISG15 can be conjugated to target proteins (ISGylation) via the stepwise action of E1, E2, and E3 enzymes. Conjugated ISG15 can be removed (deISGylated) from target proteins by USP18 (ubiquiti...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1023982
更新日期:2015-04-03 00:00:00
abstract::Autophagy is a complex, multi-step and biologically important pathway mediated by autophagosomes and autolysosomes. Accurately dissecting and detecting different stages of autophagy is important to elucidate its molecular mechanism and thereby facilitate the discovery of pharmaceutical molecules. We herein reported a ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.24241
更新日期:2013-06-01 00:00:00
abstract::Autophagy has recently been implicated in the host defense against the intracellular protozoan pathogen, Toxoplasma gondii, a major opportunistic pathogen of the central nervous system in immunosuppressed individuals. In both IFN gamma-activated macrophages and astrocytes, the p47 GTPases traffic to the T. gondii para...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.2.7637
更新日期:2009-02-01 00:00:00
abstract::Autophagy helps to maintain cellular homeostasis by removing misfolded proteins and damaged organelles, and generally acts as a cytoprotective mechanism for neuronal survival. Here we showed that mice deficient in the Vici syndrome gene Epg5, which is required for autophagosome maturation, show accumulation of ubiquit...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1238554
更新日期:2016-12-01 00:00:00
abstract::Autophagy is a highly conserved homeostatic pathway that plays an important role in tumor development and progression by acting on cancer cells in a cell-autonomous mechanism. However, the solid tumor is not an island, but rather an ensemble performance that includes nonmalignant stromal cells, such as macrophages. A ...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.26927
更新日期:2014-02-01 00:00:00
abstract::Breast cancer tissue contains a small population of cells that have the ability to self-renew; these cells are known as cancer stem-like cells (CSCs). We have recently shown that autophagy is essential for the tumorigenicity of these CSCs. Salinomycin (Sal), a K (+) /H (+) ionophore, has recently been shown to be at l...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.23997
更新日期:2013-05-01 00:00:00
abstract::Atg8 and its homologs are essential for autophagosome formation in various species. In animal cells, Atg8 homologs have an additional function in clearance of damaged organelles and bacteria, acting as a landmark for selective autophagy. We have recently shown that OATL1, a Rab-GTPase-activating protein (Rab-GAP), is ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.7.9.16178
更新日期:2011-09-01 00:00:00
abstract::This study summarizes our most recent findings on the mechanisms underlying the cadmium-induced death of mesangial cells, which leads to nephrotoxicity. Multiple pathways participate in cadmium-induced nephrotoxicity. In the ROS-GSK-3beta autophagy pathway, cadmium induces ROS most likely from the mitochondria, and th...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.4.8311
更新日期:2009-05-01 00:00:00
abstract::The Atg1/ULK1 complex plays a central role in starvation-induced autophagy, integrating signals from upstream sensors such as MTOR and AMPK and transducing them to the downstream autophagy pathway. Much progress has been made in the last few years in understanding the mechanisms by which the complex is regulated throu...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.23323
更新日期:2013-02-01 00:00:00
abstract::In a series of studies into the fate of endothelial cells exposed to non-enzymatically glycated collagen I, a model of cytotoxic molecules relevant to diabetic vasculopathy, we demonstrate that cells either undergo apoptosis or become prematurely senescent despite relatively spared telomeres and telomerase activity. O...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5904
更新日期:2008-05-01 00:00:00
abstract::Ridding neurons of toxic misfolded proteins is a critical feature of many neurodegenerative diseases. We have recently reported that lack of access of nuclear polyglutamine-expanded androgen receptor (AR) to the autophagic degradation pathway is a critical point in pathogenesis. When mutant AR is contained within the ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.8.9726
更新日期:2009-11-01 00:00:00
abstract::The uptake and degradation of cytoplasmic material by vacuolar autophagy in plants has been studied extensively by electron microscopy and shown to be involved in developmental processes such as vacuole formation, deposition of seed storage proteins and senescence, and in the response of plants to nutrient starvation ...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.2092
更新日期:2006-01-01 00:00:00
abstract::Formation of the autophagosome is likely the most complex step of macroautophagy, and indeed it is the morphological and functional hallmark of this process; accordingly, it is critical to understand the corresponding molecular mechanism. Atg8 is the only known autophagy-related (Atg) protein required for autophagosom...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.19385
更新日期:2012-05-01 00:00:00