scholarly journals E3 Ubiquitin Ligase TRIM Proteins, Cell Cycle and Mitosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 510 ◽  
Author(s):  
Santina Venuto ◽  
Giuseppe Merla
Keyword(s):  
Cell Cycle ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Ubiquitin Ligases ◽  
Cell Protein ◽  
E3 Ubiquitin Ligases ◽  
Daughter Cells ◽  
Protein Ubiquitination ◽  
Functional Units ◽  
Trim Proteins

The cell cycle is a series of events by which cellular components are accurately segregated into daughter cells, principally controlled by the oscillating activities of cyclin-dependent kinases (CDKs) and their co-activators. In eukaryotes, DNA replication is confined to a discrete synthesis phase while chromosome segregation occurs during mitosis. During mitosis, the chromosomes are pulled into each of the two daughter cells by the coordination of spindle microtubules, kinetochores, centromeres, and chromatin. These four functional units tie chromosomes to the microtubules, send signals to the cells when the attachment is completed and the division can proceed, and withstand the force generated by pulling the chromosomes to either daughter cell. Protein ubiquitination is a post-translational modification that plays a central role in cellular homeostasis. E3 ubiquitin ligases mediate the transfer of ubiquitin to substrate proteins determining their fate. One of the largest subfamilies of E3 ubiquitin ligases is the family of the tripartite motif (TRIM) proteins, whose dysregulation is associated with a variety of cellular processes and directly involved in human diseases and cancer. In this review we summarize the current knowledge and emerging concepts about TRIMs and their contribution to the correct regulation of cell cycle, describing how TRIMs control the cell cycle transition phases and their involvement in the different functional units of the mitotic process, along with implications in cancer progression.

scholarly journals Molecular Evolution, Neurodevelopmental Roles and Clinical Significance of HECT-Type UBE3 E3 Ubiquitin Ligases

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2455
Author(s):  
Mateusz C. Ambrozkiewicz ◽  
Katherine J. Cuthill ◽  
Dermot Harnett ◽  
Hiroshi Kawabe ◽  
Victor Tarabykin
Keyword(s):  
Current Knowledge ◽  
Neurological Diseases ◽  
Ubiquitin Ligases ◽  
Autism Spectrum ◽  
E3 Ubiquitin Ligases ◽  
Protein Ubiquitination ◽  
Cellular Context ◽  
Cortical Circuit ◽  
Higher Cognitive Functions ◽  
Evolutionary Emergence

Protein ubiquitination belongs to the best characterized pathways of protein degradation in the cell; however, our current knowledge on its physiological consequences is just the tip of an iceberg. The divergence of enzymatic executors of ubiquitination led to some 600–700 E3 ubiquitin ligases embedded in the human genome. Notably, mutations in around 13% of these genes are causative of severe neurological diseases. Despite this, molecular and cellular context of ubiquitination remains poorly characterized, especially in the developing brain. In this review article, we summarize recent findings on brain-expressed HECT-type E3 UBE3 ligases and their murine orthologues, comprising Angelman syndrome UBE3A, Kaufman oculocerebrofacial syndrome UBE3B and autism spectrum disorder-associated UBE3C. We summarize evolutionary emergence of three UBE3 genes, the biochemistry of UBE3 enzymes, their biology and clinical relevance in brain disorders. Particularly, we highlight that uninterrupted action of UBE3 ligases is a sine qua non for cortical circuit assembly and higher cognitive functions of the neocortex.

scholarly journals TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 820
Author(s):  
Lorena Kumarasinghe ◽  
Lu Xiong ◽  
Maria Adelaida Garcia-Gimeno ◽  
Elisa Lazzari ◽  
Pascual Sanz ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Genetic Diseases ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Lafora Disease ◽  
C Terminus ◽  
Rare Genetic Diseases ◽  
Tripartite Motif ◽  
Trim Proteins ◽  
Ring E3

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Here, we revmniew the function of these two related E3 ubiquitin ligases discussing their intrinsic and possible common pathophysiological pathways.

scholarly journals The Janus Face of p53-Targeting Ubiquitin Ligases

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1656 ◽  
Author(s):  
Qian Hao ◽  
Yajie Chen ◽  
Xiang Zhou
Keyword(s):  
Cancer Progression ◽  
Ubiquitin Ligases ◽  
Tp53 Gene ◽  
Mutant P53 ◽  
E3 Ubiquitin Ligases ◽  
Tumor Suppressor P53 ◽  
Wild Type ◽  
Cell Growth Arrest ◽  
Cancer Cell Survival ◽  
P53 Status

The tumor suppressor p53 prevents tumorigenesis and cancer progression by maintaining genomic stability and inducing cell growth arrest and apoptosis. Because of the extremely detrimental nature of wild-type p53, cancer cells usually mutate the TP53 gene in favor of their survival and propagation. Some of the mutant p53 proteins not only lose the wild-type activity, but also acquire oncogenic function, namely “gain-of-function”, to promote cancer development. Growing evidence has revealed that various E3 ubiquitin ligases are able to target both wild-type and mutant p53 for degradation or inactivation, and thus play divergent roles leading to cancer cell survival or death in the context of different p53 status. In this essay, we reviewed the recent progress in our understanding of the p53-targeting E3 ubiquitin ligases, and discussed the potential clinical implications of these E3 ubiquitin ligases in cancer therapy.

scholarly journals Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 801-811 ◽  
Author(s):  
Stephane Brunet ◽  
Bernard Maro
Keyword(s):  
Cell Cycle ◽  
Intermediate Phase ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Meiotic Maturation ◽  
Time And Space ◽  
Daughter Cells ◽  
Large Oocyte ◽  
Polar Bodies ◽  
Cytostatic Factor

During meiotic maturation of mammalian oocytes, two successive divisions occur without an intermediate phase of DNA replication, so that haploid gametes are produced. Moreover, these two divisions are asymmetric, to ensure that most of the maternal stores are retained within the oocyte. This leads to the formation of daughter cells with different sizes: the large oocyte and the small polar bodies. All these events are dependent upon the dynamic changes in the organization of the oocyte cytoskeleton (microtubules and microfilaments) and are highly regulated in time and space. We review here the current knowledge of the interplay between the cytoskeleton and the cell cycle machinery in mouse oocytes, with an emphasis on the two major activities that control meiotic maturation in vertebrates, MPF (Maturation promoting factor) and CSF (Cytostatic factor).

Epigenetic dynamics across the cell cycle

2010 ◽  
Vol 48 ◽  
pp. 107-120 ◽  
Author(s):  
Tony Bou Kheir ◽  
Anders H. Lund
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Chromatin Condensation ◽  
Chromatin Modifications ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Mammalian Cell Cycle ◽  
Regulate Cell Cycle Progression

Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle, and are shown to influence and be influenced by cell-cycle progression. Chromatin modifiers regulate cell-cycle progression locally by controlling the expression of individual genes and globally by controlling chromatin condensation and chromosome segregation. The cell cycle, on the other hand, ensures a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle.

scholarly journals E3 ubiquitin ligases: styles, structures and functions

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Quan Yang ◽  
Jinyao Zhao ◽  
Dan Chen ◽  
Yang Wang
Keyword(s):  
Cancer Progression ◽  
Large Family ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Therapeutic Approaches ◽  
E3 Ligases ◽  
Promising Target ◽  
Stress Signal ◽  
Ubiquitin Conjugating Enzyme ◽  
Almost All

AbstractE3 ubiquitin ligases are a large family of enzymes that join in a three-enzyme ubiquitination cascade together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2. E3 ubiquitin ligases play an essential role in catalyzing the ubiquitination process and transferring ubiquitin protein to attach the lysine site of targeted substrates. Importantly, ubiquitination modification is involved in almost all life activities of eukaryotes. Thus, E3 ligases might be involved in regulating various biological processes and cellular responses to stress signal associated with cancer development. Thanks to their multi-functions, E3 ligases can be a promising target of cancer therapy. A deeper understanding of the regulatory mechanisms of E3 ligases in tumorigenesis will help to find new prognostic markers and accelerate the growth of anticancer therapeutic approaches. In general, we mainly introduce the classifications of E3 ligases and their important roles in cancer progression and therapeutic functions.

scholarly journals Ubiquitin signaling in cell cycle control and tumorigenesis

2020 ◽  
Author(s):  
Fabin Dang ◽  
Li Nie ◽  
Wenyi Wei
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Kinase Inhibitors ◽  
Cell Cycle Control ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Cycle Progression ◽  
Precise Control ◽  
Cycle Regulation

Abstract Cell cycle progression is a tightly regulated process by which DNA replicates and cell reproduces. The major driving force underlying cell cycle progression is the sequential activation of cyclin-dependent kinases (CDKs), which is achieved in part by the ubiquitin-mediated proteolysis of their cyclin partners and kinase inhibitors (CKIs). In eukaryotic cells, two families of E3 ubiquitin ligases, anaphase-promoting complex/cyclosome and Skp1-Cul1-F-box protein complex, are responsible for ubiquitination and proteasomal degradation of many of these CDK regulators, ensuring cell cycle progresses in a timely and precisely regulated manner. In the past couple of decades, accumulating evidence have demonstrated that the dysregulated cell cycle transition caused by inefficient proteolytic control leads to uncontrolled cell proliferation and finally results in tumorigenesis. Based upon this notion, targeting the E3 ubiquitin ligases involved in cell cycle regulation is expected to provide novel therapeutic strategies for cancer treatment. Thus, a better understanding of the diversity and complexity of ubiquitin signaling in cell cycle regulation will shed new light on the precise control of the cell cycle progression and guide anticancer drug development.

scholarly journals E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingshuang Wang ◽  
Jiawen Dai ◽  
Youqin Zeng ◽  
Jinlin Guo ◽  
Jie Lan
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Ubiquitin Ligases ◽  
Breast Cancer Metastasis ◽  
Biological Behavior ◽  
E3 Ubiquitin Ligases ◽  
Mesenchymal Transition ◽  
Protein Ubiquitination

Female breast cancer has become the most commonly occurring cancer worldwide. Although it has a good prognosis under early diagnosis and appropriate treatment, breast cancer metastasis drastically causes mortality. The process of metastasis, which includes cell epithelial–mesenchymal transition, invasion, migration, and colonization, is a multistep cascade of molecular events directed by gene mutations and altered protein expressions. Ubiquitin modification of proteins plays a common role in most of the biological processes. E3 ubiquitin ligase, the key regulator of protein ubiquitination, determines the fate of ubiquitinated proteins. E3 ubiquitin ligases target a broad spectrum of substrates. The aberrant functions of many E3 ubiquitin ligases can affect the biological behavior of cancer cells, including breast cancer metastasis. In this review, we provide an overview of these ligases, summarize the metastatic processes in which E3s are involved, and comprehensively describe the roles of E3 ubiquitin ligases. Furthermore, we classified E3 ubiquitin ligases based on their structure and analyzed them with the survival of breast cancer patients. Finally, we consider how our knowledge can be used for E3s’ potency in the therapeutic intervention or prognostic assessment of metastatic breast cancer.

scholarly journals E3 Ubiquitin Ligases: Key Regulators of TGFβ Signaling in Cancer Progression

2021 ◽  
Vol 22 (2) ◽  
pp. 476
Author(s):  
Abhishek Sinha ◽  
Prasanna Vasudevan Iyengar ◽  
Peter ten Dijke
Keyword(s):  
Signaling Pathway ◽  
Cancer Progression ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Ubiquitin Ligases ◽  
Specific Cell ◽  
Type I ◽  
E3 Ubiquitin Ligases ◽  
Tgfβ Signaling ◽  
E3 Ligases

Transforming growth factor β (TGFβ) is a secreted growth and differentiation factor that influences vital cellular processes like proliferation, adhesion, motility, and apoptosis. Regulation of the TGFβ signaling pathway is of key importance to maintain tissue homeostasis. Perturbation of this signaling pathway has been implicated in a plethora of diseases, including cancer. The effect of TGFβ is dependent on cellular context, and TGFβ can perform both anti- and pro-oncogenic roles. TGFβ acts by binding to specific cell surface TGFβ type I and type II transmembrane receptors that are endowed with serine/threonine kinase activity. Upon ligand-induced receptor phosphorylation, SMAD proteins and other intracellular effectors become activated and mediate biological responses. The levels, localization, and function of TGFβ signaling mediators, regulators, and effectors are highly dynamic and regulated by a myriad of post-translational modifications. One such crucial modification is ubiquitination. The ubiquitin modification is also a mechanism by which crosstalk with other signaling pathways is achieved. Crucial effector components of the ubiquitination cascade include the very diverse family of E3 ubiquitin ligases. This review summarizes the diverse roles of E3 ligases that act on TGFβ receptor and intracellular signaling components. E3 ligases regulate TGFβ signaling both positively and negatively by regulating degradation of receptors and various signaling intermediates. We also highlight the function of E3 ligases in connection with TGFβ’s dual role during tumorigenesis. We conclude with a perspective on the emerging possibility of defining E3 ligases as drug targets and how they may be used to selectively target TGFβ-induced pro-oncogenic responses.

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