Abstract:
:The intrinsic apoptotic pathway is controlled by the BCL-2 family of proteins, which exhibit either a pro-death or pro-survival function. Gene knockout studies revealed that different pro-survival BCL-2 proteins are critical for the survival of distinct cell types, although overlapping functions amongst such proteins have also been identified. In the process of studying mice lacking single alleles of Mcl-1 (Mcl-1+/-), Bcl-2 (Bcl-2+/-), or both in combination (Mcl-1+/-Bcl-2+/-), we observed that Mcl-1+/-Bcl-2+/- mice weighed less when compared with their wild-type littermates as they aged. Body composition analysis demonstrated that while fat mass was similar to wild-type controls, lean mass was significantly reduced in Mcl-1+/-, Bcl-2+/-, and, most strikingly in Mcl-1+/-Bcl-2+/- mice. The weights of several tissues including the heart, tibialis anterior, and kidney were likewise reduced in Mcl-1+/-Bcl-2+/- mice. When lean mass and specific tissue weights were expressed relative to body weight, these differences were no longer significant, indicating that that Mcl-1+/-Bcl-2+/- mice, and to a lesser extent Mcl-1+/- and Bcl-2+/- mice, are smaller than their wild-type counterparts. Consistently, the anal-naso length was reduced in Mcl-1+/-Bcl-2+/- mice. While minor reductions in size were observed in female Mcl-1+/-Bcl-2+/- mice, these effects were most prominent in males. Notably, Mcl-1+/-Bcl-2+/- males had markedly smaller testes even after accounting for differences in body weight. Collectively, these data reveal that combined loss of a single allele of Mcl-1 and Bcl-2, while not overtly impairing organismal development, leads to a reduction in animal size.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Ke F,Lancaster GI,Grabow S,Murphy AJ,Strasser Adoi
10.1038/s41419-020-2376-5subject
Has Abstractpub_date
2020-03-13 00:00:00pages
185issue
3issn
2041-4889pii
10.1038/s41419-020-2376-5journal_volume
11pub_type
杂志文章abstract::The emergence of drug resistant tumours that are able to escape cell death pose a major problem in the treatment of cancers. Tumours develop resistance to DNA-damaging chemotherapeutic agents by acquiring the ability to repair their DNA. Combination therapies that induce DNA damage and disrupt the DNA damage repair pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.365
更新日期:2013-10-10 00:00:00
abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.94
更新日期:2016-04-14 00:00:00
abstract::Bone loss in postmenopausal osteoporosis is induced chiefly by an imbalance of bone-forming osteoblasts and bone-resorbing osteoclasts. Salubrinal is a synthetic compound that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Phosphorylation of eIF2α alleviates endoplasmic reticu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2159-z
更新日期:2019-12-04 00:00:00
abstract::Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 1, 3 (RIPK1, RIPK3) and mixed lineage kinase domain-like protein (MLKL). The kinase of RIPK3 phosphorylates MLKL causing MLKL to form a pore-like structure, allowing intracellular contents to release and cell dea...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.20
更新日期:2017-02-02 00:00:00
abstract::Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of N...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.132
更新日期:2017-03-23 00:00:00
abstract::The identification of specific drug targets guides the development of precise cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast cancer. We integrate the microRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0128-y
更新日期:2018-01-24 00:00:00
abstract::The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS-/-) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, inclu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1951-0
更新日期:2019-09-24 00:00:00
abstract::Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T cells associated with chronic infection by human T-cell lymphotropic virus type-1 (HTLV-1). ATLL patients with aggressive subtypes have dismal outcomes. We demonstrate that ATLL cells co-opt an early checkpoint within the tumor necrosis factor receptor ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2294-6
更新日期:2020-02-05 00:00:00
abstract::The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K componen...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.179
更新日期:2012-12-06 00:00:00
abstract::The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0843-z
更新日期:2018-07-23 00:00:00
abstract::Copious evidence demonstrates the crucial role of Rho GTPase-activating proteins in human malignancies. The downregulation of Rho GTPase-activating protein 15 (ARHGAP15), a Rac1-specific GAP, has been observed in glioma and pancreatic ductal adenocarcinoma. The present study explored the expression in colorectal cance...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0707-6
更新日期:2018-06-04 00:00:00
abstract::Myotonic dystrophy type 1 (DM1) is the most common type of adult muscular dystrophy caused by the expanded triple-nucleotides (CUG) repeats. Myoblast in DM1 displayed many defects, including defective myoblast differentiation, ribonuclear foci, and aberrant alternative splicing. Despite many were revealed to function ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03112-6
更新日期:2020-10-22 00:00:00
abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.88
更新日期:2011-09-08 00:00:00
abstract::Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.228
更新日期:2014-05-29 00:00:00
abstract::Bidirectional non-protein-coding RNAs are ubiquitously transcribed from the genome. Convergent sense and antisense transcripts may regulate each other. Here, we examined the convergent cis-noncoding rRNAs (nc-rRNAs) in A5 and E9 lung cancer models. Sense nc-rRNAs extending from rDNA intergenic region to internal trans...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.19
更新日期:2012-03-15 00:00:00
abstract::Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0015-6
更新日期:2017-12-13 00:00:00
abstract::The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. Although this proposition is supported by the clinical success of proteasome inhibitors in some malignancies, most cancers are resistant to proteasome inhibition. The ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.373
更新日期:2015-12-31 00:00:00
abstract::Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress are paradoxically implicated in myocardial ischemia/reperfusion (I/R) injury and cardioprotection. However, the precise interpretation for the dual roles of ROS and its relationship with the ER stress during I/R remain elusive. Here we investigated th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.267
更新日期:2014-06-19 00:00:00
abstract::Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Dry AMD is characterized by a progressive macular degeneration of the retinal pigment epithelium (RPE) and photoreceptors, and the RPE oxidative damage/dystrophy is at the core of the disease. Recent population/patients-based stud...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2216-7
更新日期:2020-01-13 00:00:00
abstract::Arachidonic acid (AA) is largely released during injury, but it has not been fully studied yet how AA modulates wound repair with stem cells. Therefore, we investigated skin wound-healing effect of AA-stimulated human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in vivo and its molecular mechanism i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.114
更新日期:2015-05-07 00:00:00
abstract::Mitochondrial reactive oxygen species (mtROS) homeostasis plays an essential role in preventing oxidative injury in endothelial cells, an initial step in atherogenesis. Resveratrol (RSV) possesses a variety of cardioprotective activities, however, little is known regarding the effects of RSV on mtROS homeostasis in en...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.530
更新日期:2014-12-18 00:00:00
abstract::Since publication of this paper, the authors have noticed that there were errors in Fig. 2A (the GAPDH of Mel-CV, Mel-CV.S, Mel-RMu and Mel-RMu.S), Fig. 2C (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3F (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3J(the GAPDH of Mel-RMu.S), Fig. 5C (the ERK1/2 of patient#3(post)), and...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-1301-2
更新日期:2019-03-05 00:00:00
abstract::Vascular endothelial growth factor receptor (VEGFR) and neuropilins (NRPs), a co-receptor of VEGF, play a key role in the formation and development of blood vessels and in tumour growth and metastasis. However, whether VEGFR1/2 and NRP1 are regulated by the same upstream mechanism is unclear, especially in gastric can...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2428-x
更新日期:2020-04-17 00:00:00
abstract::Cancer stem cells (CSCs) represent a population of cancer cells that possess unique self-renewal and differentiation characteristics required for tumorigenesis and are resistant to chemotherapy-induced apoptosis. Lung CSCs can be enriched by several markers including drug-resistant side population (SP), CD133(pos) and...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.93
更新日期:2012-07-19 00:00:00
abstract::The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2461-9
更新日期:2020-04-20 00:00:00
abstract::The original version of this Article contained an error in Fig. 1, in which a number of incorrect fluorescence images were inadvertently incorporated into the panel. This has been corrected in both the PDF and HTML versions of the Article. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-1422-7
更新日期:2019-03-12 00:00:00
abstract::The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.242
更新日期:2013-08-01 00:00:00
abstract::It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.122
更新日期:2014-04-10 00:00:00
abstract::Protein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose rev...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1349-z
更新日期:2019-01-25 00:00:00
abstract::Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2064-5
更新日期:2019-10-28 00:00:00