Abstract:
:TAF6δ is a pro-apoptotic splice variant of the RNA polymerase II general transcription factor, TAF6, that can dictate life vs. death decisions in animal cells. TAF6δ stands out from classical pro-apoptotic proteins because it is encoded by a gene that is essential at the cellular level, and because it functions as a component of the basal transcription machinery. TAF6δ has been shown to modulate the transcriptome landscape, but it is not known if changes in gene expression trigger apoptosis nor which TAF6δ-regulated genes contribute to cell death. Here we used microarrays to interrogate the genome-wide impact of TAF6δ on transcriptome dynamics at temporal resolution. The results revealed changes in pro-apoptotic BH3-only mitochondrial genes that correlate tightly with the onset of cell death. These results prompted us to test and validate a role for the mitochondrial pathway by showing that TAF6δ expression causes cytochrome c release into the cytoplasm. To further dissect the mechanism by which TAF6δ drives apoptosis, we pinpointed BIM and NOXA as candidate effectors. siRNA experiments showed that both BIM and NOXA contribute to TAF6δ-dependent cell death. Our results identify mitochondrial effectors of TAF6δ-driven apoptosis, thereby providing the first of mechanistic framework underlying the atypical TAF6δ apoptotic pathway's capacity to intersect with the classically defined apoptotic machinery to trigger cell death.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Delannoy A,Wilhelm E,Eilebrecht S,Alvarado-Cuevas EM,Benecke AG,Bell Bdoi
10.1038/s41419-017-0115-3subject
Has Abstractpub_date
2018-01-22 00:00:00pages
70issue
2issn
2041-4889pii
10.1038/s41419-017-0115-3journal_volume
9pub_type
杂志文章abstract::Melanoma is a kind of tumor that originates from melanocytes and is characterized by chemoresistance and distant metastasis. Although the complete pathogenesis of melanoma remains unclear, increasing evidence suggests that circular RNAs (circRNAs) may be involved. In the present study, we identified a circular RNA, ci...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2444-x
更新日期:2020-04-23 00:00:00
abstract::Although many articles have uncovered that Wnt signaling is involved in radioresistance, the mechanism is rarely reported. Here we generated two radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells ECA109 and Kyse150. We then found that Wnt signaling activity was higher in radioresistant cel...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0466-4
更新日期:2018-04-01 00:00:00
abstract::The acquisition of MDR1-mediated chemoresistance poses a major obstacle to the success of conventional chemotherapeutic agents. HSF1 is also involved in chemoresistance, and several studies have demonstrated the relationship between HSF1 and MDR1 but without any consistent results. Paclitaxel- and doxorubicin-resistan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2600-3
更新日期:2020-05-26 00:00:00
abstract::Phosphatase and tensin homolog (PTEN) regulates apoptosis and axonal growth in the developing and adult central nervous system (CNS). Here, we show that human PTEN C-terminal PDZ interactions play a critical role in neuronal apoptosis and axon regeneration after traumatic CNS injury and stroke, highlighted by the find...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1802-z
更新日期:2019-07-29 00:00:00
abstract::A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03151-z
更新日期:2020-11-06 00:00:00
abstract::Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2249-y
更新日期:2020-01-23 00:00:00
abstract::Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells expose...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1728-5
更新日期:2019-06-20 00:00:00
abstract::As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in T...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02821-2
更新日期:2020-08-18 00:00:00
abstract::Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The role of MGL in tumorigenesis remains to be fully elucidated. We have previously shown that MGL expression was reduced or absent in multiple human malignancies, and overexpression of MGL inhibited cancer cell growth. Here, we have generated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0188-z
更新日期:2018-01-18 00:00:00
abstract::Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1306-x
更新日期:2019-01-25 00:00:00
abstract::Systemic inflammatory response syndromes (SIRS) may be caused by both infectious and sterile insults, such as trauma, ischemia-reperfusion or burns. They are characterized by early excessive inflammatory cytokine production and the endogenous release of several toxic and damaging molecules. These are necessary to figh...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.70
更新日期:2014-03-06 00:00:00
abstract::Glucocorticoids (GCs) represent an important component of modern treatment regimens for fludarabine-refractory or TP53-defective chronic lymphocytic leukemia (CLL). However, GC therapy is not effective in all patients. The molecular mechanisms responsible for GC-induced apoptosis and resistance were therefore investig...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.102
更新日期:2012-08-16 00:00:00
abstract::HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome represents a life-threatening pregnancy disorder with high fetal and maternal mortality, but its underlying molecular mechanisms remain unknown. Although apoptosis has been implicated in HELLP syndrome, its pathogenic role remains largely unclear. In th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.408
更新日期:2013-10-24 00:00:00
abstract::A cell-in-cell process refers to the invasion of one living cell into another homotypic or heterotypic cell. Different from non-apoptotic death processes of internalized cells termed entosis or cannibalism, we previously reported an apoptotic cell-in-cell death occurring during heterotypic cell-in-cell formation. In t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.352
更新日期:2013-10-10 00:00:00
abstract::Adipogenesis is a process which induces or represses many genes in a way to drive irreversible changes of cell phenotypes; lipid accumulation, round cell-shape, secreting many adipokines. As a master transcription factor (TF), PPARγ2 induces several target genes to orchestrate these adipogenic changes. Thus induction ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1249-7
更新日期:2019-01-08 00:00:00
abstract::Glioblastoma multiforme (GBM) are resistant to TNFα-induced apoptosis and blockade of TNFα-induced NF-κB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-κB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.10
更新日期:2012-02-09 00:00:00
abstract::Resistin is an adipokine that is associated with obesity, inflammation, and various cancers. Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. VEGF-A is a critical angiogenic factor that is known to promote angiogenesis and metastasis in chondrosarcoma. It is unknown as to whether resistin ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1241-2
更新日期:2019-01-10 00:00:00
abstract::The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-018-0834-0
更新日期:2018-07-16 00:00:00
abstract::DNA damage regulated autophagy modulator 1 (DRAM1) is a stress-inducible regulator of autophagy and cell death. DRAM1 has been implicated in cancer, myocardial infarction, and infectious diseases, but the molecular and cellular functions of this transmembrane protein remain poorly understood. Previously, we have propo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2477-1
更新日期:2020-04-24 00:00:00
abstract::Epigenetic alteration of tumor suppression gene is one of the most significant indicators in human esophageal squamous cell carcinoma (ESCC). In this study, we identified a novel ESCC hypermethylation biomarker ZNF132 by integrative computational analysis to comprehensive genome-wide DNA methylation microarray dataset...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1236-z
更新日期:2018-12-18 00:00:00
abstract::Natural-food-based compounds show substantial promise for prevention and biotherapy of cancers including leukemia. In general, their mechanism of action remains unclear, hampering rational use of these compounds. Herein we show that the common dietary flavonoid apigenin has anticancer activity, but also may decrease c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2009.18
更新日期:2010-01-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) are a prominent component of the pro-tumoral response. The phenotype of and mechanisms used by MDSCs is heterogeneous and requires more precise characterization in gastric cancer (GC) patients. Here, we have identified a novel subset of CD45+CD33lowCD11bdim MDSCs in the periphe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0803-7
更新日期:2018-07-09 00:00:00
abstract::The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.51
更新日期:2017-02-23 00:00:00
abstract::Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of cancer stem cell (CSC) markers, and high ALDH1 expression has been related to drug resistance and facilitated tumor growth. In this study, we investigated the potential involvement of nuclear factor erythroid 2-like 2 (NFE2L2/NRF2) in CSC-like properties of ALDH-high ovar...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0903-4
更新日期:2018-08-30 00:00:00
abstract::The rapid, typically all-or-none process of mitochondrial outer membrane permeabilization (MOMP) constitutes a primary cell death decision that is controlled by the Bcl-2 family interactome. However, how strict all-or-none MOMP decisions are governed by and emanate from the dynamic interplay of pro- and antiapoptotic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0464-6
更新日期:2018-04-01 00:00:00
abstract::Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2367-6
更新日期:2020-03-13 00:00:00
abstract::Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03375-z
更新日期:2021-01-21 00:00:00
abstract::Skeletal muscle atrophy is one of the clinical symptoms of myotonic dystrophy type 1 (DM1). A decline in skeletal muscle regeneration is an important contributor to muscle atrophy. Skeletal muscle satellite cells (SSCs) drive skeletal muscle regeneration. Increased autophagy can reduce the proliferative capacity of SS...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02756-8
更新日期:2020-07-18 00:00:00
abstract::Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.437
更新日期:2014-10-30 00:00:00
abstract::Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. However, the precise ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1244-z
更新日期:2018-12-11 00:00:00