Ubiquitin Signaling in Ovarian Cancer: From Potential to Challenges

Ubiquitin proteasome system (UPS) is an emerging arena in cancer intervention. Dysregulation of various UPS components has been implicated with many cancers, and this knowledge is starting to be exploited for its role in cancer initiation, progression, and therapeutics. UPS regulates both protein turnover and non-proteolytic regulatory function of the proteins involved in cell cycle, signal transduction, DNA repair, histone modi- fication, and transcription. In addition, chromosomal aberrations and genomic alterations often present in the cancer cell genomes lead to excess of conformationally challenged aggregation-prone proteins and proteotoxic stress that make cancer cells more dependent on UPS-mediated protein degradation than normal cells. This proposition is the basis of the clinical use of proteasome inhibitor, Bortezomib, to treat multiple myeloma and mantle cell lymphoma targeting cancer cells and mostly sparing the normal cells. This chapter provides an overview of various components of UPS which are implicated in cancer and regulate ubiquitin-mediated oncogenic signaling in ovarian cancer.

• Publication year

  2018

• Venue

  Ovarian Cancer - From Pathogenesis to Treatment

• Publication date

  2018-10-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.5772/INTECHOPEN.75485
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Cancer statistics, 2017

  2017cited by this paper
• The importance of regulatory ubiquitination in cancer and metastasis

  2017influential reference
• It's Totally Tubular....Riding The New Wave of Ovarian Cancer Research.

  2016influential reference
• CDDO-Me reveals USP7 as a novel target in ovarian cancer cells

  2016cited by this paper
• MDM2 is a potential therapeutic target and prognostic factor for ovarian clear cell carcinomas with wild type TP53

  2016cited by this paper
• Proteasome Inhibitor MG132 Enhances Sensitivity to Cisplatin on Ovarian Carcinoma Cells In Vitro and In Vivo

  2016cited by this paper
• Hypoxic control of metastasis

  2016cited by this paper
• Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer

  2016cited by this paper
• Assembly of an Evolutionarily Conserved Alternative Proteasome Isoform in Human Cells.

  2016influential reference
• Ubiquitin modifications

  2016cited by this paper
• Amplification of USP13 drives ovarian cancer metabolism

  2016influential reference
• UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α

  2015cited by this paper
• Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy.

  2015cited by this paper
• Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

  2015influential reference
• The prognostic of p27kip1 in ovarian cancer: a meta-analysis

  2015cited by this paper
• Regulation of Mutant p53 Protein Expression

  2015influential reference
• Tumorigenesis and peritoneal colonization from fallopian tube epithelium

  2015influential reference
• SKP2/P27Kip1 pathway is associated with Advanced Ovarian Cancer in Saudi Patients.

  2015cited by this paper
• Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.

  2014cited by this paper
• Molecular Pathways Molecular Pathways : Translational Potential of Deubiquitinases as Drug Targets

  2014cited by this paper
• The regulation of MDM2 oncogene and its impact on human cancers.

  2014cited by this paper
• Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy

  2014cited by this paper
• Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: A preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial

  2014cited by this paper
• Effect of BRCA1 on epidermal growth factor receptor in ovarian cancer

  2013cited by this paper
• Role of ubiquitin ligases and the proteasome in oncogenesis: novel targets for anticancer therapies.

  2013cited by this paper
• Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression

  2013cited by this paper
• Ubiquitin E3 Ligase CRL4CDT2/DCAF2 as a Potential Chemotherapeutic Target for Ovarian Surface Epithelial Cancer*

  2013cited by this paper
• Correction: Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression

  2013cited by this paper
• Tumor suppressor functions of FBW7 in cancer development and progression

  2012cited by this paper
• The expression and prognosis of FOXO3a and Skp2 in human ovarian cancer

  2012cited by this paper
• Deubiquitinases in cancer: new functions and therapeutic options

  2012cited by this paper
• Targeting EGFR and PI3K pathways in ovarian cancer

  2012cited by this paper
• HECT and RING finger families of E3 ubiquitin ligases at a glance

  2012influential reference
• Integrated Genomic Analyses of Ovarian Carcinoma

  2011cited by this paper
• An Atlas of Altered Expression of Deubiquitinating Enzymes in Human Cancer

  2011cited by this paper
• Ubiquitin networks in cancer.

  2011cited by this paper
• p53 regulation by ubiquitin

  2011cited by this paper
• The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling

  2010cited by this paper
• Cullins and cancer.

  2010cited by this paper
• Ovarian cancer development and metastasis.

  2010influential reference
• The role of BRCA1 in DNA damage response

  2010cited by this paper
• Therapeutic strategies within the ubiquitin proteasome system

  2010cited by this paper
• The biology of ovarian cancer: new opportunities for translation

  2009cited by this paper
• Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis

  2009cited by this paper
• Targeting the Epidermal Growth Factor Receptor in Epithelial Ovarian Cancer: Current Knowledge and Future Challenges

  2009cited by this paper
• Ovarian cancer.

  2009cited by this paper
• Differential display identifies overexpression of the USP36 gene, encoding a deubiquitinating enzyme, in ovarian cancer

  2008cited by this paper
• Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study.

  2008cited by this paper
• The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy

  2008cited by this paper
• Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response

  2008cited by this paper
• Sporadic epithelial ovarian cancer: clinical relevance of BRCA1 inhibition in the DNA damage and repair pathway.

  2008cited by this paper
• The potential of proteasome inhibitors in cancer therapy

  2008cited by this paper
• The ubiquitin E3 ligase activity of BRCA1 and its biological functions

  2008influential reference
• Proteasome inhibitors sensitize ovarian cancer cells to TRAIL induced apoptosis

  2007cited by this paper
• Cyclin/cdk complexes: Their involvement in cell cycle progression and mitotic division

  2007cited by this paper
• Options available for profiling small samples: a review of sample amplification technology when combined with microarray profiling

  2006cited by this paper
• Protein degradation by the ubiquitin-proteasome pathway in normal and disease states.

  2006cited by this paper
• Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis.

  2006cited by this paper
• BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.

  2006cited by this paper
• Silencing of the UCHL1 gene in human colorectal and ovarian cancers

  2006cited by this paper
• The ubiquitin-proteasome pathway and its role in cancer.

  2005cited by this paper
• BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian.

  2005cited by this paper
• Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer.

  2005cited by this paper
• MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.

  2005cited by this paper
• Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage

  2004cited by this paper
• Monoubiquitination: The Signal for p53 Nuclear Export?

  2004cited by this paper
• Mass Spectrometric and Mutational Analyses Reveal Lys-6-linked Polyubiquitin Chains Catalyzed by BRCA1-BARD1 Ubiquitin Ligase*

  2004cited by this paper
• Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex

  2003cited by this paper
• BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting

  2003cited by this paper
• Skp2 overexpression is a prognostic factor in patients with ovarian adenocarcinoma.

  2003cited by this paper
• The BRCA1/BARD1 Heterodimer Assembles Polyubiquitin Chains through an Unconventional Linkage Involving Lysine Residue K6 of Ubiquitin*

  2003influential reference
• PGP9.5 overexpression in esophageal squamous cell carcinoma.

  2003cited by this paper
• BRCA1 Directs a Selective p53-Dependent Transcriptional Response towards Growth Arrest and DNA Repair Targets

  2002cited by this paper
• BRCA1 RING Domain Cancer-predisposing Mutations

  2001cited by this paper
• Mechanisms underlying ubiquitination.

  2001cited by this paper
• ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks*

  2001cited by this paper
• BRCA1 can stimulate gene transcription by a unique mechanism

  2000cited by this paper
• Cell-cycle dysregulation in breast cancer: breast cancer therapies targeting the cell cycle.

  2000cited by this paper
• p27 in Cell Cycle Control and Cancer

  2000cited by this paper
• SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27

  1999cited by this paper
• DNA copy number losses in human neoplasms.

  1999cited by this paper
• Deregulated cyclin E induces chromosome instability

  1999cited by this paper
• Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.

  1999cited by this paper
• Controlled Dimerization of ErbB Receptors Provides Evidence for Differential Signaling by Homo- and Heterodimers

  1999cited by this paper
• c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor.

  1998influential reference
• The murine gene p27Kip1 is haplo-insufficient for tumour suppression

  1998cited by this paper
• Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation.

  1996cited by this paper
• The role of controlled proteolysis in cell-cycle regulation.

  1996cited by this paper
• Activation of cyclin E/CDK2 is coupled to site‐specific autophosphorylation and ubiquitin‐dependent degradation of cyclin E.

  1996cited by this paper
• Cancer statistics

  1989cited by this paper
• Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis.

  1980cited by this paper
• Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24.

  1977cited by this paper
• Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells.

  1975cited by this paper

• The role of E3 ligases and deubiquitinases in PD-L1 regulation and the tumor microenvironment in renal cell carcinoma

  2025cites this paper
• Quantitative structure-activity relationship and molecular docking studies on human proteasome inhibitors for anticancer activity targeting NF-κB signaling pathway

  2020cites this paper
• Understanding and Targeting Apoptotic Pathways in Ovarian Cancer

  2019cites this paper