Abstract：
:SRC-3/AIB1 (Amplified in Breast Cancer-1) is a nuclear receptor coactivator for the estrogen receptor in breast cancer cells. It is also an intrinsically disordered protein when not engaged with transcriptional binding partners and degraded upon transcriptional coactivation. Given the amplified expression of SRC-3 in breast cancers, the objective of this study was to determine how increasing SRC-3 protein levels are regulated in MCF-7 breast cancer cells. We found that endogenous SRC-3 was expelled from the nucleus in vesicle-like spheres under normal growth conditions suggesting that this form of nuclear exclusion of SRC-3 is a homeostatic mechanism for regulating nuclear SRC-3 protein. Only SRC-3 not associated with CREB-binding protein (CBP) was extruded from the nucleus. We found that overexpression in MCF-7 cells results in aneuploid senescence and cell death with frequent formation of nuclear aggregates which were consistently juxtaposed to perinuclear microtubules. Transfected SRC-3 was SUMOylated and caused redistribution of nuclear promyelocytic leukemia (PML) bodies and perturbation of the nuclear membrane lamin B1, hallmarks of nucleophagy. Increased SRC-3 protein-induced autophagy and resulted in SUMO-1 localization to the nuclear membrane and formation of protrusions variously containing SRC-3 and chromatin. Aspects of SRC-3 overexpression and toxicity were recapitulated following treatment with clinically relevant agents that stabilize SRC-3 in breast cancer cells. We conclude that amplified SRC-3 levels have major impacts on nuclear protein quality control pathways and may mark cancer cells for sensitivity to protein stabilizing therapeutics.
journal_name
Cellsjournal_title
Cellsauthors
Cabrita MA,Renart LI,Lau R,Pratt MACdoi
10.3390/cells8101278subject
Has Abstractpub_date
2019-10-19 00:00:00issue
10issn
2073-4409pii
cells8101278journal_volume
8pub_type
杂志文章相关文献
Cells文献大全abstract：:Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B bind...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8111391
更新日期：2019-11-05 00:00:00
abstract：:Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted the...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8050481
更新日期：2019-05-20 00:00:00
abstract：:Radiotherapy is one of the major cancer treatment strategies. Exposure to penetrating radiation causes cellular stress, directly or indirectly, due to the generation of reactive oxygen species, DNA damage, and subcellular organelle damage and autophagy. These radiation-induced damage responses cooperatively contribute...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8091105
更新日期：2019-09-18 00:00:00
abstract：:Cannabidiol (CBD), as the only phytocannabinoid that has no psychoactive effect, has both antioxidant and anti-inflammatory effects, and thus might be suggested as a cytoprotective compound against UV-induced metabolic changes in skin cells. Therefore, the aim of this study was to investigate the level of protective C...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8090995
更新日期：2019-08-28 00:00:00
abstract：:The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated sele...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9112416
更新日期：2020-11-04 00:00:00
abstract：:The disease course of myelodysplastic syndromes (MDS) features chromosome instability and clonal evolution, leading to the sequential acquisition of novel cytogenetic aberrations and the accumulation of these abnormalities in the bone marrow. Although clonal cytogenetic abnormalities can be detected by conventional cy...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8040304
更新日期：2019-04-02 00:00:00
abstract：:Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease characterized by both motor and nonmotor features. The diagnose of PD is based on a review of patients' signs and symptoms, and neurological and physical examinations. So far, no tests have been devised that can conclusively diagnose PD. In t...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells7120245
更新日期：2018-12-05 00:00:00
abstract：:Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have been identified as...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9010079
更新日期：2019-12-28 00:00:00
abstract：:Previously, we used a lentiviral vector to deliver furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to t...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9102227
更新日期：2020-10-02 00:00:00
abstract：:Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and dif...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells10010025
更新日期：2020-12-25 00:00:00
abstract：:Specific nuclear sub-compartments that are regions of fundamental processes such as gene expression or DNA repair, contain phosphoinositides (PIPs). PIPs thus potentially represent signals for the localization of specific proteins into different nuclear functional domains. We performed limited proteolysis followed by ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells10010068
更新日期：2021-01-04 00:00:00
abstract：:During strong parallel fiber stimulation, glutamate released at parallel fiber-Purkinje cell synapses activates type-1 metabotropic glutamate receptor (mGluR1) to trigger a slow excitatory postsynaptic current (sEPSC) in cerebellar Purkinje neurons. The sEPSC is mediated by transient receptor potential canonical 3 (TR...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells7080090
更新日期：2018-07-29 00:00:00
abstract：:Chemotherapeutic targeting of microtubules has been the standard of care in treating a variety of malignancies for decades. During mitosis, increased microtubule dynamics are necessary for mitotic spindle formation and successful chromosomal segregation. Microtubule targeting agents (MTAs) disrupt the dynamics necessa...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8040346
更新日期：2019-04-12 00:00:00
abstract：OBJECTIVES:Synovial fluids of rheumatoid arthritis (RA) patients commonly contain high concentrations of soluble CD14 (sCD14). To investigate its potential role in RA pathogenesis, we tested whether sCD14 binding transmits a signal to fibroblast-like synoviocytes from RA patients (RA-FLS). METHODS:The induction of pro...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9071689
更新日期：2020-07-14 00:00:00
abstract：:Blood vessel formation or angiogenesis is a key process for successful tooth regeneration. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) possess paracrine proangiogenic properties, which are, at least partially, induced by their extracellular vesicles (EVs). However, the isolation of BM-MSCs is associated wi...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9020312
更新日期：2020-01-28 00:00:00
abstract：:CircRNA is a type of closed circular non-coding RNA formed by reverse splicing and plays an important role in regulating the growth and development of plants and animals. To investigate the function of circ-FoxO3 in mouse myoblast cells' (C2C12) differentiation and proliferation, we used RT-qPCR to detect the expressi...
journal_title：Cells
pub_type： 杂志文章,收录出版
doi：10.3390/cells8060616
更新日期：2019-06-19 00:00:00
abstract：:Sarcopenia, a syndrome commonly seen in elderly populations, is often characterized by a gradual loss of skeletal muscle, leading to the decline of muscle strength and physical performance. Growing evidence suggests that the prevalence of sarcopenia increases in patients with heart failure (HF), which is a dominant pa...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9102284
更新日期：2020-10-13 00:00:00
abstract：:Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8111469
更新日期：2019-11-19 00:00:00
abstract：:A critically ill polytrauma patient is one of the most complex cases to be admitted to the intensive care unit, due to both the primary traumatic complications and the secondary post-traumatic interactions. From a molecular, genetic, and epigenetic point of view, numerous biochemical interactions are responsible for t...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells7120271
更新日期：2018-12-13 00:00:00
abstract：:A new epoch is emerging with intense research on nutraceuticals, i.e., "food or food product that provides medical or health benefits including the prevention and treatment of diseases", such as Alzheimer's disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuropro...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9112347
更新日期：2020-10-23 00:00:00
abstract：:Extracellular vesicles (EVs) contribute to a variety of signaling processes and the overall physiological and pathological states of stem cells and tissues. Human induced pluripotent stem cells (hiPSCs) have unique characteristics that can mimic embryonic tissue development. There is growing interest in the use of EVs...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8090993
更新日期：2019-08-28 00:00:00
abstract：:Rac1 is a small GTPase that belongs to the Rho family. The Rho family of small GTPases is a subfamily of the Ras superfamily. The Rho family of GTPases mediate a plethora of cellular effects, including regulation of cytoarchitecture, cell size, cell adhesion, cell polarity, cell motility, proliferation, apoptosis/surv...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells7120263
更新日期：2018-12-11 00:00:00
abstract：:The maternal nutritional status is essential to the health and well-being of the fetus. Maternal protein restriction during the perinatal stage causes sperm alterations in the offspring that are associated with epididymal dysfunctions. Vascular endothelial growth factor (VEGF) and its receptor, VEGFr-2, as well as aqu...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8091094
更新日期：2019-09-17 00:00:00
abstract：:Hsp60 is a molecular chaperone classically described as a mitochondrial protein with multiple roles in health and disease, participating to the maintenance of protein homeostasis. It is well known that skeletal muscle is a complex tissue, rich in proteins, that is, subjected to continuous rearrangements, and this home...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells7120224
更新日期：2018-11-22 00:00:00
abstract：:Over a decade ago, the formation of neutrophil extracellular traps (NETs) was described as a novel mechanism employed by neutrophils to tackle infections. Currently applied methods for NETs release quantification are often limited by the use of unspecific dyes and technical difficulties. Therefore, we aimed to develop...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9020508
更新日期：2020-02-24 00:00:00
abstract：:Cholangiocarcinoma (CCA) is a highly invasive and metastatic form of carcinoma with bleak prognosis due to limited therapies, frequent relapse, and chemotherapy resistance. There is an urgent need to identify the molecular regulators of CCA in order to develop novel therapeutics and advance diseases diagnosis. Many ce...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9030780
更新日期：2020-03-23 00:00:00
abstract：:Liver fibrosis is a common feature of sustained liver injury and represents a major public health problem worldwide. Fibrosis is an active research field and discoveries in the last years have contributed to the development of new antifibrotic drugs, although none of them have been approved yet. Liver sinusoidal endot...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9040929
更新日期：2020-04-10 00:00:00
abstract：:Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed. It is also known to be linked with several aspects of tumor malignancy in some types of human tumors, including invasion, metastasis, and cancer stemness. However, there are few reports on the expression of dog PDPN (dPDPN) in ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9051136
更新日期：2020-05-05 00:00:00
abstract：:The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic, with more than 50 million cases reported globally. Findings have consistently identified an increased severity of SARS-CoV-2 infection in individuals with diabetes. Osteopontin, a...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9112528
更新日期：2020-11-23 00:00:00
abstract：:Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9122579
更新日期：2020-12-02 00:00:00
