Abstract:
:WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC) and it accelerates cell proliferation in NSCLC. However, the detailed mechanism underlying the role of WDR79 in the proliferation of NSCLC cells remains unclear. Here, we report the discovery of a molecular interaction between WDR79 and USP7 and show its functional significance in linking the Mdm2-p53 pathway to the proliferation of NSCLC cells. We found that WDR79 colocalized and interacted with USP7 in the nucleus of NSCLC cells. This event, in turn, reduced the ubiquitination of Mdm2 and p53, thereby increasing the stability and extending the half-life of the two proteins. We further found that the functional effects of WDR79 depended upon USP7, because the knockdown of USP7 resulted in their attenuation. Finally, we demonstrated that WDR79 promoted the proliferation of NSCLC cells via USP7. Taken together, our findings reveal a novel molecular function of WDR79 and may lead to broadly applicable and innovative therapeutic avenues for NSCLC.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Sun Y,Cao L,Sheng X,Chen J,Zhou Y,Yang C,Deng T,Ma H,Feng P,Liu J,Tan W,Ye Mdoi
10.1038/cddis.2017.162subject
Has Abstractpub_date
2017-04-13 00:00:00pages
e2743issue
4issn
2041-4889pii
cddis2017162journal_volume
8pub_type
杂志文章abstract::We reported previously that adult (HRAS-/-; NRAS-/-) double knockout (DKO) mice showed no obvious external phenotype although lower-than-expected numbers of weaned DKO animals were consistently tallied after crossing NRAS-KO and HRAS-KO mice kept on mixed genetic backgrounds. Using mouse strains kept on pure C57Bl/6 b...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2075-2
更新日期:2019-11-04 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::B-cell lymphoma-2 (Bcl-2) proteins mediate intrinsic-, or mitochondrial-, initiated apoptosis. We have investigated the structure and function of the least characterized Bcl-2 family member, Bcl-B, solving the crystal structure of a Bcl-B:Bim complex to 1.9 Å resolution. Bcl-B is distinguished from other Bcl-2 family ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.178
更新日期:2012-12-13 00:00:00
abstract::Increasing the sensitivity of glioblastoma cells to radiation is a promising approach to improve survival in patients with glioblastoma multiforme (GBM). This study aims to determine if serine/threonine phosphatase (protein phosphatase 6 (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM orthot...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.126
更新日期:2011-12-08 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::Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.509
更新日期:2014-11-27 00:00:00
abstract::Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic al...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.185
更新日期:2012-12-20 00:00:00
abstract::Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), mainly activates prosurvival pathways, including protection from apoptosis. In this work, we investigated the cardioprotective mechanisms of Met activation by agonist monoclonal antibodies (mAbs). Cobalt chloride (CoCl2), a chemical mimetic of hypox...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.155
更新日期:2014-04-17 00:00:00
abstract::Pin1 is the only known peptidyl-prolyl cis-trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cel...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-018-0844-y
更新日期:2018-08-29 00:00:00
abstract::Mesenchymal stem cells (MSCs) have been reported to localize in colorectal carcinomas, and participate in the formation of the tumor microenvironment. They have recently been isolated from colorectal cancer tissues, and are implicated in the growth, invasion, and metastasis of cancer cells. However, the roles and deta...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0176-3
更新日期:2018-01-18 00:00:00
abstract::Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer's disease, catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediates cellular K+ efflux as an early step in the apoptotic cascade. Sin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.529
更新日期:2014-12-11 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for pat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.391
更新日期:2014-10-02 00:00:00
abstract::The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1-4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, D...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2016.408
更新日期:2016-12-08 00:00:00
abstract::Protein S-nitrosylation, the redox-based posttranslational modification of a cysteine thiol by the attachment of a nitric oxide (NO) group, is responsible for a variety of signaling effects. Dysregulation of S-nitrosylation may be directly linked to cancer apoptotic resistance and cancer therapy outcomes, emphasizing ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1561-x
更新日期:2019-04-15 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::Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to dat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0348-9
更新日期:2018-02-22 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendip...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.178
更新日期:2014-05-08 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::The mechanism of pathological osteogenesis in Ankylosing spondylitis (AS) is largely unknown. Our previous studies demonstrated that the imbalance between BMP-2 and Noggin secretion induces abnormal osteogenic differentiation of marrow-derived mesenchymal stem cells (MSCs) from AS patients in a two-dimensional culture...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1586-1
更新日期:2019-04-25 00:00:00
abstract::Back pain is a leading cause of global disability and is strongly associated with intervertebral disc (IVD) degeneration (IDD). Hallmarks of IDD include progressive cell loss and matrix degradation. The Akt signaling pathway regulates cellularity and matrix production in IVDs and its inactivation is known to contribut...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1985-3
更新日期:2019-10-03 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::Therapeutic resistance of neoplasms is mainly attributed to gradual evolution of mutational profile1. Here, we demonstrate a microRNA-mediated mechanism that effectively improves fitness of SKBR3 mammary carcinoma cells by cytoplasmic reprogramming. The reprogramming is triggered by endogenous miR4673 transcribed from...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1088-6
更新日期:2018-10-19 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic (DA) neurons in the substantia nigra (SN); however, the underlying molecular mechanisms remain to be fully elucidated. In this study, we found that the expression level of transcription factor Six...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.120
更新日期:2016-05-05 00:00:00
abstract::Cancer-associated fibroblasts (CAFs), a dominant component of the pancreatic tumor microenvironment, are mainly considered as promotors of malignant progression, but the underlying molecular mechanism remains unclear. Here, we show that SDF-1 secreted by CAFs stimulates malignant progression and gemcitabine resistance...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1104-x
更新日期:2018-10-18 00:00:00
abstract::The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.443
更新日期:2017-01-05 00:00:00
abstract::Disrupting microtubule dynamics with spindle poisons activates the spindle-assembly checkpoint (SAC) and induces mitotic cell death. However, mitotic exit can occur prematurely without proper chromosomal segregation or cytokinesis by a process termed mitotic slippage. It remains controversial whether mitotic slippage ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1539-8
更新日期:2019-04-05 00:00:00
abstract::The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.61
更新日期:2015-03-26 00:00:00
abstract::The subversion of the normal function exerted by the cellular prion protein (PrP(C)) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.195
更新日期:2013-01-10 00:00:00
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 c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.61
更新日期:2013-03-07 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