Abstract:
:The ubiquitination-proteasome and degradation system is an essential process that regulates protein homeostasis. This system is involved in the regulation of cell proliferation, differentiation and survival, and dysregulations in this system lead to pathologies including cancers. The ubiquitination system is an enzymatic cascade that mediates the marking of target proteins by an ubiquitin label and thereby directs their degradation through the proteasome pathway. The ubiquitination of proteins occurs through a three-step process involving ubiquitin activation by the E1 enzyme, allowing for the transfer to a ubiquitin-conjugated enzyme E2 and to the targeted protein via ubiquitin-protein ligases (E3), the most abundant group of enzymes involved in ubiquitination. Significant advances have been made in our understanding of the role of E3 ubiquitin ligases in the control of bone turnover and tumorigenesis. These ligases are implicated in the regulation of bone cells through the degradation of receptor tyrosine kinases, signaling molecules and transcription factors. Initial studies showed that the E3 ubiquitin ligase c-Cbl, a multi-domain scaffold protein, regulates bone resorption by interacting with several molecules in osteoclasts. Further studies showed that c-Cbl controls the ubiquitination of signaling molecules in osteoblasts and in turn regulates osteoblast proliferation, differentiation and survival. Recent data indicate that c-Cbl expression is decreased in primary bone tumors, resulting in excessive receptor tyrosine kinase signaling. Consistently, c-Cbl ectopic expression reduces bone tumorigenesis by promoting tyrosine kinase receptor degradation. Here, we review the mechanisms of action of E3 ubiquitin ligases in the regulation of normal and pathologic bone formation, and we discuss how targeting the interactions of c-Cbl with some substrates may be a potential therapeutic strategy to promote osteogenesis and to reduce tumorigenesis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Sévère N,Dieudonné FX,Marie PJdoi
10.1038/cddis.2012.217subject
Has Abstractpub_date
2013-01-17 00:00:00pages
e463issn
2041-4889pii
cddis2012217journal_volume
4pub_type
杂志文章,评审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::Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::The glutamate-induced excitotoxicity pathway has been reported in several neurodegenerative diseases. Molecules that inhibit the release of glutamate or cause the overactivation of glutamate receptors can minimize neuronal cell death in these diseases. Osmotin, a homolog of mammalian adiponectin, is a plant protein fr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.538
更新日期:2014-01-30 00:00:00
abstract::Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent stat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03074-9
更新日期:2020-10-14 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
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abstract::The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was pos...
journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1716-9
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1647-5
更新日期:2019-06-03 00:00:00
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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
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.51
更新日期:2016-03-17 00:00:00
abstract::Mitochondrial apoptosis-inducing factor (AIF) influences the oxidative phosphorylation (OXPHOS) system and can be recruited as a mediator of cell death. Pathogenic mutations in the AIFM1 gene cause severe human diseases. Clinical manifestations include inherited peripheral neuropathies, prenatal cerebral abnormalities...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.170
更新日期:2015-07-09 00:00:00
abstract::Caveolin-1 (CAV1) is a crucial regulator of lipid accumulation and metabolism. Previous studies have shown that global Cav1 deficiency affects lipid metabolism and hepatic steatosis. We aimed to analyze the consequences of hepatocyte-specific Cav1 knockout under healthy conditions and upon non-alcoholic fatty liver di...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2295-5
更新日期:2020-02-06 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::Long non-coding RNA (lncRNA) plays an important role in the development of human malignant tumours. Recently, an increasing number of lncRNAs have been identified and investigated in a variety of tumours. However, the expression pattern and biological function of lncRNAs in cervical cancer still remain largely unexplo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1228-z
更新日期:2018-12-05 00:00:00
abstract::Highly conserved microRNA-9 (miR-9) has a critical role in various cellular processes including neurogenesis. However, its regulation by neurotropins that are known to mediate neurogenesis remains poorly defined. In this study, we identify platelet-derived growth factor-BB (PDGF-BB)-mediated upregulation of miR-9, whi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.486
更新日期:2013-12-12 00:00:00
abstract::Gastric cancer (GC) ranks among the top five malignant tumors worldwide by the incidence and mortality rate. However, the mechanisms underlying its progression are poorly understood. In this study, we investigated the role of SIRT1, a class III deacetylase, in the invasion and metastasis of GC. Here, we found that kno...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1033-8
更新日期:2018-09-24 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02864-5
更新日期:2020-08-19 00:00:00
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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::Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02860-9
更新日期:2020-08-14 00:00:00
abstract::Mitochondrial dysfunction and synaptic damage are critical early features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and τ. We previously reported that the scaffolding protein RanBP9, which is overall increased in AD, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.203
更新日期:2013-01-24 00:00:00
abstract::The majority of developmentally programmed cell death (PCD) is mediated by caspase-dependent apoptosis; however, additional modalities, including autophagy-dependent cell death, have important spatiotemporally restricted functions. Autophagy involves the engulfment of cytoplasmic components in a double membrane vesicl...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1368-9
更新日期:2019-02-08 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.38
更新日期:2015-02-26 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.554
更新日期:2017-10-26 00:00:00
abstract::The peptide/histidine transporter SLC15A3 is responsible for transporting histidine, certain dipeptide and peptidomimetics from inside the lysosome to cytosol. Previous studies have indicated that SLC15A3 transcripts are mainly expressed in the lymphatic system, however, its regulation and biological role in innate im...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0809-1
更新日期:2018-07-10 00:00:00
abstract::Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's diseas...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0508-y
更新日期:2018-05-01 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::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::Epidermal keratinocyte differentiation on the body surface is a carefully choreographed process that leads to assembly of a barrier that is essential for life. Perturbation of keratinocyte differentiation leads to disease. Activator protein 1 (AP1) transcription factors are key controllers of this process. We have sho...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.21
更新日期:2015-02-19 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.332
更新日期:2016-12-01 00:00:00
abstract::Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02848-5
更新日期:2020-08-12 00:00:00