Abstract:
:The homolog of p53 gene, p63, encodes multiple p63 protein isoforms. TAp63 proteins contain an N-terminal transactivation domain similar to that of p53 and function as tumor suppressors; whereas ΔNp63 isoforms, which lack the intact N-terminal transactivation domain, are associated with human tumorigenesis. Accumulating evidence demonstrating the important roles of p63 in development and cancer development, the regulation of p63 proteins, however, is not fully understood. In this study, we show that peptidyl-prolyl isomerase Pin1 directly binds to and stabilizes TAp63α and ΔNp63α via inhibiting the proteasomal degradation mediated by E3 ligase WWP1. We further show that Pin1 specifically interacts with T538P which is adjacent to the P550PxY543 motif, and disrupts p63α-WWP1 interaction. In addition, while Pin1 enhances TAp63α-mediated apoptosis, it promotes ΔNp63α-induced cell proliferation. Furthermore, knockdown of Pin1 in FaDu cells inhibits tumor formation in nude mice, which is rescued by simultaneous knockdown of WWP1 or ectopic expression of ΔNp63α. Moreover, overexpression of Pin1 correlates with increased expression of ΔNp63α in human oral squamous cell carcinoma samples. Together, these results suggest that Pin1-mediated modulation of ΔNp63α may have a causative role in tumorigenesis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Li C,Chang DL,Yang Z,Qi J,Liu R,He H,Li D,Xiao ZXdoi
10.1038/cddis.2013.468subject
Has Abstractpub_date
2013-12-05 00:00:00pages
e943issn
2041-4889pii
cddis2013468journal_volume
4pub_type
杂志文章abstract::The ubiquitin E3 ligase DELTEX1 (DTX1) is specifically downregulated in gastric cancer tissues, and expression of DTX1 is linked to better prognoses and survival in gastric cancer. Cellular FLICE inhibitory protein (c-FLIP) is known for its pivotal role in the resistance of cancer cells to death receptor-induced cell ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0165-6
更新日期:2018-01-26 00:00:00
abstract::The high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were establishe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1898-1
更新日期:2019-09-10 00:00:00
abstract::Aberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the program driving progre...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0933-y
更新日期:2018-08-29 00:00:00
abstract::Current practices for the therapy of chondrosarcoma, including wide-margin surgical resection and chemotherapy, are less than satisfactory. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) have an essential role in the initiation and progression of tumors. As a typical lncRNA, HOTAIR is...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.31
更新日期:2017-02-09 00:00:00
abstract::Interferon gamma (IFNγ) is a key moderator of cell-mediated immunity with diverse, mainly pro-inflammatory actions on immunocytes and target tissue. Recent studies have shown it may enhance anti-tumor and antiviral effects of CD8 T cells. Here we investigate the mechanisms by which IFNγ mediates CD8 T-cell cytotoxic f...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.67
更新日期:2017-06-01 00:00:00
abstract::Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell fu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0894-1
更新日期:2018-09-05 00:00:00
abstract::Correction to: NPG Asia Materials (2018) https://doi.org/10.1038/s41427-018-0014-9 published online on 16 April 2018. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-018-0639-1
更新日期:2018-05-24 00:00:00
abstract::MicroRNAs have emerged as important post-transcriptional regulators of gene expression and are involved in diverse diseases and cellular process. Decreased expression of miR-181a has been observed in the patients with coronary artery disease, but its function and mechanism in atherogenesis is not clear. This study was...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1599-9
更新日期:2019-05-07 00:00:00
abstract::The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. We elucidated this interesting question in pancreatic ductal adenocarcinoma, which...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.157
更新日期:2016-06-02 00:00:00
abstract::Microglia serve as the innate immune cells of the central nervous system (CNS) by providing continuous surveillance of the CNS microenvironment and initiating defense mechanisms to protect CNS tissue. Upon injury, microglia transition into an activated state altering their transcriptional profile, transforming their m...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03084-7
更新日期:2020-10-23 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::The mechanism by which tumor-associated macrophages (TAMs) affect cancer progression is not fully understood. This study developed a microfluidic-based co-culture device to mimic the tumor microenvironment to assess TAM effects on invasion and metastasis in NSCLC. The results showed lung carcinoma cells could cause ma...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1618-x
更新日期:2019-05-16 00:00:00
abstract::Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substituti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1333-7
更新日期:2019-02-11 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::Synovial sarcoma is a highly aggressive but rare form of soft tissue malignancy that primarily affects the extremities of the arms or legs, for which current chemotherapeutic agents have not been proven to be very effective. The cyclin-dependent kinase 4/6-retinoblastoma protein (CDK4/6-Rb) pathway of cell cycle contr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0474-4
更新日期:2018-05-01 00:00:00
abstract::Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.161
更新日期:2017-04-06 00:00:00
abstract::Vascularization deficiency caused a lot of diseases, such as diabetes ulcer and myocardial infarction. Mesenchymal stem cells (MSCs), with the self-renewal and multipotent differentiation capacities, have been used for many diseases treatment through regulation microenvironment. Numerous studies reported that MSCs tra...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0082-8
更新日期:2018-01-19 00:00:00
abstract::Phenothiazines are a family of heterocyclic compounds whose clinical utility includes treatment of psychiatric disorders as well as chemotherapy-induced emesis. Various studies have demonstrated that these compounds possess cytotoxic activities in tumor cell lines of different origin. However, there is considerable co...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.56
更新日期:2014-03-13 00:00:00
abstract::KLF5 is frequently deleted and downregulated in prostate cancer, and recently it has been reported that KLF5 loss is enriched in the aggressive branches of prostate cancer evolution. However, why KLF5 loss is associated with prostate cancer aggressiveness is still not clear. Herein, we analyzed KLF5 expression in TCGA...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2671-1
更新日期:2020-06-16 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::Functional neuronal circuits require a constant remodeling of their network composed of highly interconnected neurons. The plasticity of synapses and the shaping of elaborated dendritic branches are energy demanding and therefore depend on an efficient mitochondrial oxidative phosphorylation (OXPHOS). The spatial and ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.144
更新日期:2014-04-10 00:00:00
abstract::During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.37
更新日期:2013-02-28 00:00:00
abstract::Polo-like kinase 1 (PLK1) is an important mitotic kinase and its expression is tightly regulated in the cell cycle and in the DNA damage response. PLK1 expression is previously shown to be suppressed by p53 and/or p21. Here, we demonstrate that the CCAAT box in the PLK1 promoter is pivotal for p53/p21-mediated PLK1 re...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.527
更新日期:2014-01-09 00:00:00
abstract::Bu-Shen-Ning-Xin Decoction (BSNXD) administration has alleviated the early pathologic damage of atherosclerosis by inhibiting the adhesion molecule expression and upregulating the estrogen receptor (ER) β expression in endothelial cells, and increasing the serum nitric oxide (NO) level without any effect on serum lipi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.66
更新日期:2013-03-21 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::Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1933-2
更新日期:2019-09-17 00:00:00
abstract::We have previously shown that the combination of statins and taxanes was a powerful trigger of HGT-1 human gastric cancer cells' apoptosis1. Importantly, several genes involved in the "Central carbon metabolism pathway in cancer", as reported in the Kyoto Encyclopedia of Genes and Genomes, were either up- (ACLY, ERBB2...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0761-0
更新日期:2018-07-03 00:00:00
abstract::Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used in the clinic for bone defect reconstruction because of its powerful osteoinductive capacity. However, commercially available rhBMP-2 requires a high concentration in the clinical setting for consistent bone formation. A high dose of rhBMP-2 induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0126-0
更新日期:2018-02-02 00:00:00
abstract::The tumor suppressor p53 has critical roles in regulating lipid metabolism, but whether and how p53 regulates cardiolipin (CL) de novo biosynthesis is unknown. Here, we report that p53 physically interacts with histone deacetylase SIRT6 in vitro and in vivo, and this interaction increases following palmitic acid (PA) ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0984-0
更新日期:2018-09-20 00:00:00
abstract::Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03176-4
更新日期:2020-11-11 00:00:00