Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options

Mourtzoukou, Despoina; Drikos, Ioannis; Goutas, Nikolaοs; Vlachodimitropoulos, Dimitrios

doi:10.5772/intechopen.72600

Cited by 3 publications

(3 citation statements)

References 130 publications

(155 reference statements)

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“…The activity of ubiquitin ligases and deubiquitinase enzymes maintains the oncogenic pathways (Gallo et al, 2017) which might control cancer initiation, progression, or promotion. Several regulatory pathways, such as the negative feedback mechanism of p53 protein, are controlled by the ubiquitination process in breast cancer (Mourtzoukou et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro

Hayal¹,

Doğan²,

Şişli³

et al. 2020

Turk J Biol

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Because breast cancer is complicated at the pathological, histological, clinical, and molecular levels, identification of new genetic targets against carcinogenic pathways is required to generate clinically relevant treatment options. In the current study, ubiquitin-specific protease 7 (USP7), which regulates various cellular pathways including Mdm2, p53, and NF–κB, was selected as a potential gene editing strategy for breast cancer in vitro. Anticancer activity of USP7 gene suppression has been evaluated through cell proliferation, gene expression, cell cycle, sphere dissemination, and cell migration analysis. Here, siRNA and shRNA strategies and an allosteric small-molecule inhibitor of USP7 were used to define potential anticancer activity against MCF7 and T47D human breast cancer cell lines. Both blockage of deubiquitination by p5091 and knockdown of USP7 reduced cell proliferation, cell migration, colony formation, and sphere dissemination for both MCF7 and T47D breast cancer cell lines. Restriction of USP7 activity strongly enhanced apoptotic gene expression and reduced metastatic ability of breast cancer cell lines. This study describes one potential molecular target for the suppression of breast cancer proliferation and metastasis. Identification of USP7 as a promising gene editing candidate might open up the possibility of new molecular drug research in targeting the ubiquitination pathway in cancer.

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Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro

Hayal¹,

Doğan²,

Şişli³

et al. 2020

Turk J Biol

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“…Both monomers and polymers control the fate of proteins to which they become covalently attached. Protein (poly) ubiquitination has been linked to many cellular processes, including protein degradation (Chau et al, 1989), endocytosis (Boname et al, 2010;Goto et al, 2010), DNA repair (Chen & Chen, 2013) and tumor morphology (Mourtzoukou, Drikos, Goutas, & Vlachodimitropoulos, 2018). Numerous other functions have been linked to Ub and are explored in a review by Swatek and Komander (2016).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the topology of ubiquitin chains

Geis-Asteggiante

Lee

Fenselau

2019

Methods in Enzymology

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The small protein ubiquitin and its multiple polymers are encountered free in cells and as posttranslational modifications on all proteins. Different polyubiquitin three dimensional structures are shown to correlate uniquely with different cellular functions as part of the diverse ubiquitin signaling. At the same time, this multiplicity of structures provides serious challenges to the analytical biochemist. Globally applicable strategies are presented here for the analyses of polyubiquitins and of ubiquitinated proteins, which take advantage of the speed, specificity and sensitivity of top-down tandem mass spectrometry. Particular attention is given to the supervised interpretation of fragmentation as revealed in the MS/MS spectra of these branched proteins. The strategy is compatible with any MS activation technology, is applicable to all polyubiquitin linkage and chain types, can be extended to ubiquitin-like proteins, and will be compatible with and enhanced by continuing advances in LC-MS/MS instrumentation and interpretation software.

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“…Components of the ubiquitin system are often dysregulated, contributing to numerous diseases. Recently conducted analyses indicate that ubiquitin plays a pivotal part in multiple signaling and cell regulatory events in malignancies, including but not limited to gynecological [ 47 ] and breast cancer, which remain the most common carcinoma and second cause of premature death amongst women globally [ 48 , 49 ]. This may suggest the possibility of this gender-dependent elevation in concentrations of ubiquitin being related to the above findings.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin Is Not a Blood Biomarker of an Early Cognitive Decline in the Polish Elderly

McFarlane

Kozakiewicz

Wojciechowska

et al. 2023

CIMB

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Together with development of new pharmaceutical interventions, as well as the introduction of the concept of initial dementia phase, the demand for early diagnosis has been growing. Research on potential blood biomarkers, amazingly attractive, mainly due to the facility of deriving the material, has provided ambiguous results throughout. The existence of an association between ubiquitin and Alzheimer’s disease pathology suggests that it could be a potential neurodegeneration biomarker. The present study aims to identify and assess the relationship between ubiquitin with regard to the adequacy as a biomarker of an initial dementia and cognitive decline in the elderly. Method: The study sample was composed of 230 participants: 109 women and 121 men aged 65 and older. The relationships of plasma ubiquitin levels with cognitive performance, gender, and age were analyzed. The assessments were performed in three groups of cognitive functioning level: cognitively normal, mild cognitive impairment, and mild dementia, of which the subjects were divided with the Mini-Mental State Examination (MMSE). Results: No significant disparities in plasma ubiquitin levels for various levels of cognitive functioning were identified. Significantly higher plasma ubiquitin levels in women were found in comparison to men. No significant differences were found in ubiquitin concentrations based on age. Results suggest that ubiquitin does not meet the requirements for qualification as a blood biomarker of an early cognitive decline. In order to thoroughly evaluate the potential of research on ubiquitin in connection to an early neurodegenerative process, further studies are needed.

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Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options

Cited by 3 publications

References 130 publications

Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro

Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro

Analysis of the topology of ubiquitin chains

Ubiquitin Is Not a Blood Biomarker of an Early Cognitive Decline in the Polish Elderly

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