Abstract:
:Nutlin-3 selectively activates p53 by inhibiting the interaction of this tumor suppressor with its negative regulator murine double minute 2 (mdm2), while trichostatin A (TSA) is one of the most potent histone deacetylase (HDAC) inhibitors currently available. As both Nutlin-3 and TSA increase the levels of the cell cycle inhibitor p21(cip1/waf1) in cells, we investigated whether a combination of these compounds would further augment p21 levels. Contrary to expectations, we found that short-term exposure to Nutlin-3 and TSA in combination did not have an additive effect on p21 expression. Instead, we observed that activation of p53 prevented the ability of TSA to increase p21 levels. Furthermore, TSA inhibited Nutlin-3-induced expression of p53-dependent mRNAs including P21. This negative effect of TSA on Nutlin-3 was significantly less pronounced in the case of hdm2, another p53 downstream target. Aside from suggesting a model to explain these incompatible effects of Nutlin-3 and TSA, we discuss the implications of our findings in cancer therapy and cell reprogramming.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Sachweh MC,Drummond CJ,Higgins M,Campbell J,Laín Sdoi
10.1038/cddis.2013.61subject
Has Abstractpub_date
2013-03-07 00:00:00pages
e533issn
2041-4889pii
cddis201361journal_volume
4pub_type
杂志文章abstract::The epithelial-mesenchymal transition (EMT) of podocytes had been reported to be involved in the glomerular fibrosis in diabetic kidney diseases, which was regulated by TGFβ and NFκB pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGFβ in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1098-4
更新日期:2018-10-09 00:00:00
abstract::ZAK, a mixed lineage kinase, is often described as a positive or negative regulator of cell growth. We identified it as one of the top hits in our kinome cDNA screen for potent regulators of epithelial mesenchymal transition (EMT). Ectopic expression of ZAK promoted EMT phenotypes and apoptosis resistance in multiple ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0161-x
更新日期:2018-02-02 00:00:00
abstract::Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.300
更新日期:2017-07-27 00:00:00
abstract::Cardiac glycosides (CGs), prescribed to treat cardiovascular alterations, display potent anti-cancer activities. Despite their well-established target, the sodium/potassium (Na(+)/K(+))-ATPase, downstream mechanisms remain poorly elucidated. UNBS1450 is a hemi-synthetic cardenolide derived from 2″-oxovorusharin extrac...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.134
更新日期:2015-06-11 00:00:00
abstract::Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.200
更新日期:2015-08-06 00:00:00
abstract::Human pluripotent stem cells provide a versatile platform for regenerative studies, drug testing and disease modeling. That the expression of only four transcription factors, Oct4, Klf4, Sox2 and c-Myc (OKSM), is sufficient for generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells has ...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2015.167
更新日期:2015-07-23 00:00:00
abstract::Hepatocytes undergo the metaplasia into ductal biliary epithelial cells (BECs) in response to chronic injury, and subsequently contribute to liver regeneration. The mechanism underlying hepatocyte-to-ductal metaplasia has not been explored until now. In mouse models of liver fibrosis, a florid BEC response was observe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2372-9
更新日期:2020-03-23 00:00:00
abstract::Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung aden...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1811-y
更新日期:2019-07-30 00:00:00
abstract::Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.211
更新日期:2015-08-13 00:00:00
abstract::Despite the introduction of novel targeted therapies, chemotherapy still remains the primary treatment for metastatic melanoma in poorly funded healthcare environments or in case of disease relapse, with no reliable molecular markers for progression-free survival (PFS) available. As chemotherapy primarily eliminates c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2309-3
更新日期:2020-02-13 00:00:00
abstract::HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we dem...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0272-z
更新日期:2018-02-15 00:00:00
abstract::Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2666-y
更新日期:2020-06-11 00:00:00
abstract::We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1555-8
更新日期:2019-04-11 00:00:00
abstract::During radiologic or nuclear accidents, high-dose ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a deadly disorder that urgently needs effective therapy. Unfortunately, current treatments based on natural products and antioxidants have shown very limited effects in alleviating deadly GIS. Reserve i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2715-6
更新日期:2020-07-06 00:00:00
abstract::The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.139
更新日期:2012-10-11 00:00:00
abstract::Cellular senescence is the permanent arrest of cell cycle, physiologically related to aging and aging-associated diseases. Senescence is also recognized as a mechanism for limiting the regenerative potential of stem cells and to protect cells from cancer development. The senescence program is realized through autocrin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.445
更新日期:2013-11-07 00:00:00
abstract::Psoriasis is characterized by keratinocyte hyperproliferation. While significant progress has been made in understanding the molecular mechanism regulating the proliferation of keratinocytes, little is known about the epigenetic factors that control this process. EZH2 and EZH2 mediated trimethylation of histone H3 lys...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03028-1
更新日期:2020-10-03 00:00:00
abstract::T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yield...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2016.222
更新日期:2017-03-02 00:00:00
abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1102-z
更新日期:2018-10-15 00:00:00
abstract::Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.10
更新日期:2010-04-01 00:00:00
abstract::MicroRNAs (miRNAs) are important class of functional regulators involved in human cancers development, including colorectal cancer (CRC). Exploring aberrantly expressed miRNAs may provide us with new insights into the initiation and development of CRC by functioning as oncogenes or tumor suppressors. The aim of our st...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1188-3
更新日期:2019-02-12 00:00:00
abstract::The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington's disease (HD), a neurodegenerative disorder caused by neural death due to expa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02754-w
更新日期:2020-07-18 00:00:00
abstract::Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a recently identified gene associated with malignant tumor progression and patient chemotherapy resistance in human hepatocellular carcinoma (HCC). Previously, we found an association between CHD1L overexpression and poor patient survival in non-s...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1371-1
更新日期:2019-02-04 00:00:00
abstract::Acute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myelo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02759-5
更新日期:2020-07-20 00:00:00
abstract::Chronic psychological stress has been demonstrated to play an important role in several severe diseases, but whether it affects disease therapy or not remains unclear. Mesenchymal stem cells (MSCs) have been demonstrated to have therapeutic potentials in treating tissue injury based on their multidifferentiation poten...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.257
更新日期:2014-06-26 00:00:00
abstract::Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0154-9
更新日期:2018-01-18 00:00:00
abstract::Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.65
更新日期:2013-03-14 00:00:00
abstract::Diffusely infiltrating gliomas are among the most prognostically discouraging neoplasia in human. Temozolomide (TMZ) in combination with radiotherapy is currently used for the treatment of glioblastoma (GBM) patients, but less than half of the patients respond to therapy and chemoresistance develops rapidly. Epigeneti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.245
更新日期:2014-06-05 00:00:00
abstract::Metastasis is the leading cause of death for colorectal cancer (CRC). However, the protein transport process involved in CRC metastasis remains unclear. In this report, we use whole-exome sequencing and bioinformatics analysis to identify somatic mutations in CRC samples and found mutations of the protein transport ge...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2358-7
更新日期:2020-03-02 00:00:00
abstract::Maintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome ac...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.79
更新日期:2016-07-21 00:00:00