scholarly journals HERC Ubiquitin Ligases in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1653
Author(s):  
Joan Sala-Gaston ◽  
Arturo Martinez-Martinez ◽  
Leonardo Pedrazza ◽  
L. Francisco Lorenzo-Martín ◽  
Rubén Caloto ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Ubiquitin Ligases ◽  
Tumor Type ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Damage Response ◽  
Herc Proteins

HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies.

scholarly journals Macrophages, Inflammation, and Tumor Suppressors: ARF, a New Player in the Game

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Paqui G. Través ◽  
Alfonso Luque ◽  
Sonsoles Hortelano
Keyword(s):  
Tumor Suppressor ◽  
Immune Responses ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Macrophage Polarization ◽  
Innate Immune

The interaction between tumor progression and innate immune system has been well established in the last years. Indeed, several lines of clinical evidence indicate that immune cells such as tumor-associated macrophages (TAMs) interact with tumor cells, favoring growth, angiogenesis, and metastasis of a variety of cancers. In most tumors, TAMs show properties of an alternative polarization phenotype (M2) characterized by the expression of a series of chemokines, cytokines, and proteases that promote immunosuppression, tumor proliferation, and spreading of the cancer cells. Tumor suppressor genes have been traditionally linked to the regulation of cancer progression; however, a growing body of evidence indicates that these genes also play essential roles in the regulation of innate immunity pathways through molecular mechanisms that are still poorly understood. In this paper, we provide an overview of the immunobiology of TAMs as well as what is known about tumor suppressors in the context of immune responses. Recent advances regarding the role of the tumor suppressor ARF as a regulator of inflammation and macrophage polarization are also reviewed.

scholarly journals The Role of E3, E4 Ubiquitin Ligase (UBE4B) in Human Pathologies

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 62 ◽  
Author(s):  
Nikolaos Antoniou ◽  
Nefeli Lagopati ◽  
Dimitrios Ilias Balourdas ◽  
Michail Nikolaou ◽  
Alexandros Papalampros ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Ubiquitin Ligase ◽  
Molecular Mechanisms ◽  
Ubiquitin Ligases ◽  
Cellular Functions ◽  
P53 Expression ◽  
Damage Response ◽  
Mechanisms Of Carcinogenesis

The genome is exposed daily to many deleterious factors. Ubiquitination is a mechanism that regulates several crucial cellular functions, allowing cells to react upon various stimuli in order to preserve their homeostasis. Ubiquitin ligases act as specific regulators and actively participate among others in the DNA damage response (DDR) network. UBE4B is a newly identified member of E3 ubiquitin ligases that appears to be overexpressed in several human neoplasms. The aim of this review is to provide insights into the role of UBE4B ubiquitin ligase in DDR and its association with p53 expression, shedding light particularly on the molecular mechanisms of carcinogenesis.

scholarly journals Microtubular and Nuclear Functions of γ-Tubulin: Are They LINCed?

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 259 ◽  
Author(s):  
Jana Chumová ◽  
Hana Kourová ◽  
Lucie Trögelová ◽  
Petr Halada ◽  
Pavla Binarová
Keyword(s):  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Nuclear Organization ◽  
Linc Complex ◽  
Cellular Functions ◽  
Microtubule Nucleation ◽  
Damage Response

γ-Tubulin is a conserved member of the tubulin superfamily with a function in microtubule nucleation. Proteins of γ-tubulin complexes serve as nucleation templates as well as a majority of other proteins contributing to centrosomal and non-centrosomal nucleation, conserved across eukaryotes. There is a growing amount of evidence of γ-tubulin functions besides microtubule nucleation in transcription, DNA damage response, chromatin remodeling, and on its interactions with tumor suppressors. However, the molecular mechanisms are not well understood. Furthermore, interactions with lamin and SUN proteins of the LINC complex suggest the role of γ-tubulin in the coupling of nuclear organization with cytoskeletons. γ-Tubulin that belongs to the clade of eukaryotic tubulins shows characteristics of both prokaryotic and eukaryotic tubulins. Both human and plant γ-tubulins preserve the ability of prokaryotic tubulins to assemble filaments and higher-order fibrillar networks. γ-Tubulin filaments, with bundling and aggregating capacity, are suggested to perform complex scaffolding and sequestration functions. In this review, we discuss a plethora of γ-tubulin molecular interactions and cellular functions, as well as recent advances in understanding the molecular mechanisms behind them.

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

scholarly journals The role of SCF ubiquitin-ligase complex at the beginning of life

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiayan Xie ◽  
Yimei Jin ◽  
Guang Wang
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cellular Proteins ◽  
Cell Cycle Regulators ◽  
Signal Transducers ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin Ligase Complex ◽  
Scf Ubiquitin Ligase

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.

scholarly journals A20: a master regulator of arthritis

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongyao Wu ◽  
Xiaomin He ◽  
Ning Huang ◽  
Jiayun Yu ◽  
Bin Shao
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Mouse Models ◽  
Inflammatory Arthritis ◽  
Molecular Mechanisms ◽  
Related Research ◽  
Inflammatory Protein ◽  
New Findings ◽  
Tnf Α

Abstract A20, also known as TNF-α-induced protein 3 (TNFAIP3), is an anti-inflammatory protein that plays an important part in both immune responses and cell death. Impaired A20 function is associated with several human inflammatory and autoimmune diseases. Although the role of A20 in mediating inflammation has been frequently discussed, its intrinsic link to arthritis awaits further explanation. Here, we review new findings that further demonstrate the molecular mechanisms through which A20 regulates inflammatory arthritis, and we discuss the regulation of A20 by many factors. We conclude by reviewing the latest A20-associated mouse models that have been applied in related research because they reflect the characteristics of arthritis, the study of which will hopefully cast new light on anti-arthritis treatments.

Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

2011 ◽  
Vol 439 (3) ◽  
pp. 349-378 ◽  
Author(s):  
Anthony J. Morgan ◽  
Frances M. Platt ◽  
Emyr Lloyd-Evans ◽  
Antony Galione
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Late Endosomes ◽  
Wide Range ◽  
Health And Disease ◽  
Lysosome Related Organelles ◽  
Cellular Compartments ◽  
Endosomal Vesicles ◽  
Intracellular Targets

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

scholarly journals NFKB1 and Cancer: Friend or Foe?

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 133 ◽  
Author(s):  
Julia Concetti ◽  
Caroline L Wilson
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Multiple Roles ◽  
Current Evidence ◽  
Cellular Processes ◽  
Specific Manner ◽  
Organ Specific ◽  
A Cell ◽  
Potential Cancer

Current evidence strongly suggests that aberrant activation of the NF-κB signalling pathway is associated with carcinogenesis. A number of key cellular processes are governed by the effectors of this pathway, including immune responses and apoptosis, both crucial in the development of cancer. Therefore, it is not surprising that dysregulated and chronic NF-κB signalling can have a profound impact on cellular homeostasis. Here we discuss NFKB1 (p105/p50), one of the five subunits of NF-κB, widely implicated in carcinogenesis, in some cases driving cancer progression and in others acting as a tumour-suppressor. The complexity of the role of this subunit lies in the multiple dimeric combination possibilities as well as the different interacting co-factors, which dictate whether gene transcription is activated or repressed, in a cell and organ-specific manner. This review highlights the multiple roles of NFKB1 in the development and progression of different cancers, and the considerations to make when attempting to manipulate NF-κB as a potential cancer therapy.

scholarly journals Sex differences in severity and mortality from COVID-19: are males more vulnerable?

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajay Pradhan ◽  
Per-Erik Olsson
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Basic Research ◽  
Contributing Factors ◽  
High Infection ◽  
Males And Females

Abstract Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

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